Rat colonic lipid peroxidation and antioxidant status: the effects of dietary luteolin on 1,2-dimethylhydrazine challenge

Colon cancer is the third most common cancer and second leading cause of cancer-related death in the United States. A number of recent articles demonstrate the importance of natural products as cancer chemopreventive agents. In this study, we evaluated the chemopreventive efficacy of luteolin, a flavonoid, on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in DMH-induced experimental colon carcinogenesis. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given to the DMH-treated rats at the initiation and post-initiation stages of carcinogenesis. The animals were killed after 30 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization), tumor incidence was 100% in DMH-treated rats. In those DMH-treated rats that had received luteolin during the initiation or post-initiation stages of colon carcinogenesis, the incidence of cancer and the colon tumor size was significantly reduced as compared to that for DMH-treated rats not receiving luteolin. In the presence of DMH, relative to the results for the control rats, there were decreased levels of lipid peroxidation, as denoted by thiobarbituric acid reactive substances (TBARS), conjugated dienes and lipid hydroperoxides, decreased activities of the enzymic antioxidants superoxide dismutase (SOD) and catalase (CAT), and elevated levels of glutathione and the glutathione-dependent enzymes reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR), and of the non-enzymic antioxidants vitamin C and vitamin E. Our study shows that intragastric administration of luteolin inhibits colon carcinogenesis, not only by modulating lipid peroxidation and antioxidant status, but also by preventing DMH-induced histopathological changes. Our results thus indicate that luteolin could act as a potent chemopreventive agent for colon carcinogenesis.     

Morin augments anticarcinogenic and antiproliferative efficacy against 7,12-dimethylbenz(a)-anthracene induced experimental mammary carcinogenesis

In general, oxidative stress resulting from an imbalance between prooxidant and antioxidant systems plays an important role in the pathogenesis of cancer. Morin (3,5,7,2',4'-pentahydroxyflavone), a member of the flavanol group, has been shown to possess chemopreventive potential against hepatocellular and colon cancer in experimental animals. Given the demonstrated importance of morin, aim of the present study was to evaluate the effect of morin on antiproliferative and anticarcinogenic effect against DMBA-induced experimental mammary carcinogenesis. Oral administration of 7,12-dimethylbenz(a)-anthracene (25 mg/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and nonenzymic antioxidants (reduced glutathione, vitamin C, and vitamin E). The levels of lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides) and tumor markers such as CA 15-3, AFP and CEA in serum were increased significantly in cancer-induced animals as compared to control rats. Oral supplementation of morin at a dose of 50 mg/kg body weight significantly improved the body weight, enzymic, and nonenzymic antioxidants and considerably decreased the lipid peroxidation marker and tumor markers levels. Histological observations also correlated with the biochemical parameters. Tumor bearing animals showed marked increase in proliferating cell nuclear antigen-positive cells and also the number of AgNOR/nuclei compared with control rats while this expression levels were significantly reduced upon morin treatment. Thus, this study reveals the possible beneficial effect of morin as chemopreventive agent against the oxidative stress induced during mammary carcinogenesis.     

Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats

Antioxidants are one of the key players in tumorigenesis, several natural and synthetic antioxidants were shown to have anticancer effects. In the present investigation the efficacy of silymarin on the antioxidant status of N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in Wistar albino male rats were assessed. The animals were divided into five groups. The animals in the groups 1 and 3 were normal control and silymarin control, respectively. Groups 2, 4 and 5 were administered with 0.01% NDEA in drinking water for 15 weeks to induce hepatocellular carcinoma (HCC). Starting 1 week prior to NDEA administration group 4 animals were treated with silymarin in diet for 16 weeks, 10 weeks after NDEA administration group 5 animals were treated with silymarin and continued till the end of the experiment period (16 weeks). After the experimental period the body weight, relative liver weight, number of nodules, size of nodules, the levels of lipid peroxidation, glutathione (GSH), and the activities of antioxidant enzymes were assessed in both haemolysate and liver tissue. In group 2 hepatocellular carcinoma induced animals there was an increase in the number of nodules, relative liver weight. The levels of lipid peroxides were elevated with subsequent decrease in the body weight, (glutathione) GSH, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD). In contrast, silymarin + NDEA treated groups 4 and 5 animals showed a significant decrease in the number of nodules with concomitant decrease in the lipid peroxidation status. The levels of GSH and the activities of antioxidant enzymes in both haemolysate and liver were improved when compared with hepatocellular carcinoma induced group 2 animals. The electron microscopy studies were also carried out which supports the chemopreventive action of the silymarin against NDEA administration during liver cancer progression. These findings suggest that silymarin suppresses NDEA induced hepatocarcinogenesis by modulating the antioxidant defense status of the animals.     

Augmented efficacy of tamoxifen in rat breast tumorigenesis when gavaged along with riboflavin, niacin, and CoQ10: effects on lipid peroxidation and antioxidants in mitochondria

Reactive oxygen species (ROS) play a major role in causing mitochondrial changes linked to cancer and metastasis. Uptake of antioxidants by tissue to reduce the ROS production could be instrumental in controlling cancer. Tamoxifen (TAM), a nonsteroidal anti-estrogen drug most used in the chemotherapy and chemoprevention of breast cancer. Riboflavin, niacin and coenzyme Q10 (CoQ10) are proved to be potent antioxidants and protective agents against many diseases including cancer. The objective of this research is to determine the therapeutic efficacy of combinatorial therapy on mammary carcinoma bearing rats in terms of the mitochondrial lipid peroxidation and antioxidant status especially MnSOD. Female albino rats of Sprague-Dawley strain were selected for the investigation. Mammary carcinoma was induced with 7,12-dimethyl benz(a)anthracene (DMBA: 25 mg), and the treatment was started by the oral administration of TAM (10 mg/kg body weight/day) along with riboflavin (45 mg/kg body weight/day), niacin (100 mg/kg body weight/day) and CoQ10 (40 mg/kg body weight/day) for 28 days. The levels of lipid peroxides, activities of enzymic and non-enzymic antioxidants were measured in the mitochondria isolated from the mammary gland and liver of control and experimental rats. Rats treated with DMBA showed an increase in mitochondrial lipid peroxidation (mammary gland 52.3%; liver 25.1%) accompanied by high malondialdehyde levels along with lowered activities of mitochondrial enzymic antioxidants [superoxide dismutase (mammary gland 19.9%; liver 24.8%), catalase (mammary gland 50%; liver 19.7%), glutathione peroxidase (mammary gland 47.8%; liver 31.1%)] and non-enzymic antioxidants [reduced glutathione (mammary gland 14.3%; liver 13.3%), Vitamin C (mammary gland 6.49%; liver 21.4%) and E (mammary gland 20.3%; liver 22.2%)]. Administration of combinatorial therapy restored lipid peroxide level and the activities of enzymic and non-enzymic antioxidants to near normalcy. In addition, antitumour activity was also found to be enhanced which is evident from the increased expression of tumour suppressor gene MnSOD thereby preventing cancer cell proliferation. These results suggested that TAM treatment is the most effective during co-administration of riboflavin, niacin and CoQ10 in terms of mitochondrial antioxidant and antitumour activity.     

Activity of Cassia auriculata leaf extract in rats with alcoholic liver injury

This study was undertaken to investigate the effect of Cassia auriculata leaf extract on tissue lipid peroxidation and antioxidant status in experimental hepatotoxicity. Administering ethanol to rats for 60 days resulted in significantly elevated levels of serum total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) as compared with those of the experimental control rats. Significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), hydroperoxides and lowered activities of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were also observed on alcohol treatment as compared with those of experimental control rats. Concentration of serum non-enzymic antioxidants such as vitamin E and vitamin C were also significantly lowered on alcohol supplementation. Treatment with Cassia auriculata leaf extract at a dose of 250 mg kg(-1) body weight and 500 mg kg(-1) body weight to rats administered alcohol, lowered the levels of TBARS and hydroperoxides and elevated the activities of SOD and CAT and the levels of reduced GSH in the liver, brain, kidney and intestine significantly compared to unsupplemented alcohol treated rats. Cassia auriculata leaf extract treatment restored the serum vitamin E, and vitamin C levels also to near those of the experimental control animals. Our data indicate that supplementation with Cassia auriculata leaf extract can offer protection against free radical mediated oxidative stress in experimental hepatotoxicity. In addition, histopathological studies of the liver and brain confirmed the beneficial role of Cassia auriculata leaf extract.     

Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats

Nickel (Ni), a major environmental pollutant, is known for its wide toxic manifestations. In the present study caffeic acid (CA), one of the most commonly occurring phenolic acids in fruits, grains and dietary supplements, was evaluated for its protective effect against the Ni induced oxidative damage in liver. In this investigation, Ni (20 mg/kg body weight) was administered intraperitoneally for 20 days to induce toxicity. CA was administered orally (15, 30 and 60 mg/kg body weight) for 20 days with intraperitoneal administration of Ni. Ni induced liver damage was clearly shown by the increased activities of serum hepatic enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) along with increased elevation of lipid peroxidation indices (thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides). The toxic effect of Ni was also indicated by significantly decreased levels of enzymatic (superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (glutathione (GSH), vitamin C and vitamin E). CA administered at a dose of 60 mg/kg body weight significantly reversed the activities of hepatic marker enzymes to their near normal levels when compared with other two doses. In addition, CA significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. All these changes were supported by histological observations. The results indicate that CA may be beneficial in ameliorating the Ni induced oxidative damage in the liver of rats.     

Effect of Emblica officinalis (Gaertn) on CCl4 induced hepatic toxicity and DNA synthesis in Wistar rats

A single dose of CCl4 (1 ml/kg body weight, po in corn oil) increased the levels of SGOT (serum glutamate oxaloacetate transaminase), SGPT (serum glutamate pyruvate transaminase), LDH (lactate dehydrogenase), glutathione-S-transferase and depletion in reduced glutathione, glutathione peroxidase and glutathione reductase. It also caused enhancement in the levels of lipid peroxidation (LPO) and DNA synthesis. There was also pathological deterioration of hepatic tissue as evident from multivacuolated hepatocytes containing fat globules around central vein. The pretreatment of E. officinalis for 7 consecutive days showed a profound pathological protection to liver cell as depicted by univacuolated hepatocytes. Pretreatment with E. officinalis at doses of 100 and 200 mg/kg body weight, prior to CCl4 intoxication showed significant reduction in the levels of SGOT, SGPT, LDH, glutathione-S-transferase, LPO and DNA synthesis. There was also increase in reduced glutathione, glutathione peroxidase and glutathione reductase. The results suggest that E. officinalis inhibits hepatic toxicity in Wistar rats.     

Chemomodulatory effect of Ficus racemosa extract against chemically induced renal carcinogenesis and oxidative damage response in Wistar rats

Ferric nitrilotriacetate (Fe-NTA) is a well-known renal carcinogen. In this communication, we show the chemopreventive effect of Ficus racemosa extract against Fe-NTA-induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, gamma-glutamyl transpeptidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [(3)H] incorporation into renal DNA. It also enhances DEN (N-diethylnitrosamine) initiated renal carcinogenesis by increasing the percentage incidence of tumors. Treatment of rats orally with F. racemosa extract (200 and 400 mg/kg body weight) resulted in significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (P<0.001) and incidence of tumors. Renal glutathione content (P<0.01), glutathione metabolizing enzymes (P<0.001) and antioxidant enzymes were also recovered to significant level (P<0.001). Thus, our data suggests that F. racemosa extract is a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative damage response in Wistar rats.     

Antioxidant effect of the marine algae Chlorella vulgaris against naphthalene-induced oxidative stress in the albino rats

Alcoholic extract of the marine algae Chlorella vulgaris was examined for its free radical scavenging effect with reference to naphthalene-induced lipid peroxidation in serum, liver, and kidney of rats. Initially, upon naphthalene intoxication (435 mg/kg body weight, intraperitoneally), the lipid peroxidation activity increased significantly (P < 0.001), and in contrast, the enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymic antioxidants (glutathione, ascorbic acid, and α-tocopherol) levels decreased remarkably. When the naphthalene stressed rats were treated with Chlorella vulgaris extract (70 mg/kg body weight, orally), the lipid peroxidation activity reduced significantly (P < 0.001) and the activities of both the enzymic and non-enzymic antioxidants increased reaching near control values. The minimum concentration (70 mg/l) of the extract that exhibited maximum (85%) free radical scavenging activity was chosen for the experimental study. The present results suggest that Chlorella vulgaris extract exerts its chemo-preventive effect by modulating the antioxidants status and lipid peroxidation during naphthalene intoxication.     

Temporal variations of lipid peroxidation products, antioxidants and liver marker enzymes in experimental hyperammonemic rats

Circadian variations of lipid peroxidation products: thiobarbituric acid and reactive substances (TBARS), antioxidants: reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and liver marker enzymes such as transaminases (aspartate transaminase (AST) and alanine transaminase (ALT), alkaline phosphatase (ALP) and γ-Glutamyl transpeptidase (GGT) in circulation were analysed in control and ammonium chloride (AC) induced (100 mg/kg bodyweight) hyperammonemic rats. Elevated lipid peroxidation and liver marker enzymes (increased mesor of TBARS, AST, ALT, ALP and GGT) associated with decreased activities of antioxidants (decreased mesor of GPx, GSH, SOD and CAT) were found in hyperammonemic rats. Variations in acrophase, amplitude and r values were also found in between the control and hyperammonemic rats. These alterations clearly indicate that temporal liver marker enzymes and redox status are modulated during hyperammonemic conditions, which may also play a crucial role in disease development.     

Hepato-protective potential of carotenoid meso-zeaxanthin against paracetamol, CCl4 and ethanol induced toxicity

Hepato-protective potential of carotenoid meso-zeaxanthin [(3R, 3'S)-beta, beta-carotene-3, 3'-diol] was studied using in vivo rat models. Paracetamol (3 g/kg body wt, orally), 20% ethanol (7.5 g/kg body wt, orally) and CCl4 (2.5 ml /kg, ip) were used as hepato toxins. Levels of marker enzymes of hepatic injury such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase and alkaline phosphatase, and serum bilirubin, which were drastically elevated by these hepato toxins were significantly decreased by meso-zeaxanthin pretreatment in a dose-dependent manner. Oxidative stress markers, tissue lipid peroxidation, conjugated dienes and tissue hydroperoxides, were high in the paracetamol treated control group animals, which were lowered by meso-zeaxanthin administration. Level of glutathione and antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase, in liver tissue was increased by meso-zeaxanthin pretreatment compared to control group during alcohol and CCl4 induced hepatotoxicity. Hydroxyproline, an indicator of fibrosis in liver tissue, decreased remarkably by meso-zeaxanthin administration despite its notable elevation in ethanol treated rats. Histopathological analysis of liver tissue showed the hepatoprotective potential of meso-zeaxanthin.     

Potential chemoprevention of diethylnitrosamine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger (Zingiber zerumbet)

Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P < 0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P < 0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P < 0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P < 0.05) lowered. By the TUNEL assay, there were significantly (P < 0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.     

Anticancer effect of Limonin against benzo(a)pyrene‐induced lung carcinogenesis in Swiss albino mice and the inhibition of A549 cell proliferation through apoptotic pathway

The main purpose of the current study is to reveal the anticancer action of limonin against benzo(a)pyrene [B(a)P]‐treated lung carcinogenesis in Swiss albino mice and A549 lung cancer cells. B(a)P was orally supplemented (50 mg/kg body weight) twice a week for four weeks induction of lung cancer in mice. The lung weight, body weight, incidence of tumor, lipid peroxidation, carcinoembryonic antigen (CEA), enzymatic and nonenzymatic antioxidants (superoxide dismutase, GPx, glutathione, glutathione reductase, catalase, and glutathione S‐transferase), serum marker enzymes (aryl hydroxylase, lactate dehydrogenase, 5′‐nucleotidases, and γ‐glutamyl transpeptidase), and inflammatory mediators (interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α) were estimated. Moreover, a histopathological study of lung tissues was supported by the biochemical analysis. Furthermore, the anticancer activity of limonin on A549 cells was measured by cell viability, production of reactive oxygen species (ROS), apoptotic morphological changes by AO/EtBr staining. Additionally, the status of apoptosis protein (caspase‐9 and ‐3) expressions was analyzed by the colorimetric analysis. B(a)P‐induced mice showed increased lipid peroxidation, CEA, serum marker enzymes and inflammatory cytokines levels with simultaneously decreased in the nonenzymatic and enzymatic antioxidants levels. Limonin supplements significantly reverted back to all these changes in this manner, showing the efficiency of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of limonin‐enhanced apoptosis by loss of cell viability, improved ROS production, apoptotic morphological changes, and apoptosis protein expression were analyzed. Overall, these results suggest the anticancer potential of limonin against B(a)P‐induced lung cancer in Swiss albino mice and A549 lung cancer cells.     

Anticancer effect of selenium/chitosan/polyethylene glycol/allyl isothiocyanate nanocomposites against diethylnitrosamine-induced liver cancer in rats

BackgroundNano-based drug delivery systems have shown several advantages in cancer treatment like specific targeting of cancer cells, good pharmacokinetics, and lesser adverse effects. Liver cancer is a fifth most common cancer and third leading cause of cancer-related mortalities worldwide.ObjectiveThe present study focusses to formulate the selenium (S)/chitosan (C)/polyethylene glycol (Pg)/allyl isothiocyanate (AI) nanocomposites (SCPg-AI-NCs) and assess its therapeutic properties against the diethylnitrosamine (DEN)-induced liver cancer in rats via inhibition of oxidative stress and tumor markers.MethodologyThe SCPg-AI-NCs were synthesized by ionic gelation technique and characterized by various characterization techniques. The liver cancer was induced to the rats by injecting a DEN (200 mg/kg) on the 8th day of experiment. Then DEN-induced rats treated with 10 mg/kg of formulated SCPg-AI-NCs an hour before DEN administration for 16 weeks. The 8-hydroxy-2′ -deoxyguanosine (8-OHdG) content, albumin, globulin, and total protein were examined by standard methods. The level of glutathione (GSH), vitamin-C & -E, and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities were examined using assay kits. The liver marker enzymes i.e., alanine transaminase (ALT), aspartate tansaminase (AST), γ-glutamyl transaminase (GGT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activities, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA), Bax, and Bcl-2 levels, and caspase-3&9 activities was examined using assay kits and the liver histopathology was assessed microscopically by hematoxylin and eosin staining method. The effect of formulated SCPg-AI-NCs on the viability and apoptotic cell death on the HepG2 cells were examined using MTT and dual staining assays, respectively.ResultsThe results of different characterization studies demonstrated the formation of SCPg-AI-NCs with tetragonal shape, narrowed distribution, and size ranging from 390 to 450 nm. The formulated SCPg-AI-NCs treated liver cancer rats indicated the reduced levels of 8-OHdG, albumin, globulin, and total protein. The SCPg-AI-NCs treatment appreciably improved the GSH, vitamin-C & -E contents, and SOD, CAT, GPx, and GR activities in the serum of liver cancer rats. The SCPg-AI-NCs treatment remarkably reduced the liver marker enzyme activities in the DEN-induced rats. The SCPg-AI-NCs treatment decreased the AFP and CEA contents and enhanced the Bax and caspase 3&9 activities in the DEN-induced rats. The SCPg-AI-NCs effectively decreased the cell viability and induced apoptosis in the HepG2 cells.ConclusionThe present findings suggested that the formulated SCPg-AI-NCs remarkably inhibited the DEN-induced liver carcinogenesis in rats. These findings provide an evidence that SCPg-AI-NCs can be a promising anticancer nano-drug in the future to treat the liver carcinogenesis.     

The effect of dimethyl dimethoxy biphenyl dicarboxylate (DDB) against tamoxifen-induced liver injury in rats: DDB use is curative or protective

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.     

Protective effect of Cassia fistula Linn. on diethylnitrosamine induced hepatocellular damage and oxidative stress in ethanol pretreated rats

Diethylnitrosamine (DEN), found in many commonly consumed foods, is widely reported to induce cancer in animals and humans. The aim of the present study was to investigate the hepatoprotective and antioxidant activities of the leaf extract of the medicinal plant Cassia fistula Linn. against diethylnitrosamine induced liver injury in ethanol pretreated rats. Albino Wistar rats, pretreated with ethanol for 15 days, were administered a single dose of DEN. Thirty days after DEN administration, hepatotocellular damage was observed histologically, along with elevated levels of serum AST, ALT, ALP, LDH, γ-GT and bilirubin and a simultaneous fall in the levels of the marker enzymes in the liver tissue. Liver oxidative stress was confirmed by elevated levels of lipid peroxidation (LPO) and a decrease in enzymic and non-enzymic antioxidants activities. Oral administration of the ethanolic leaf extract (ELE) of Cassia fistula for 30 days to ethanol + DEN treated rats significantly improved the above alterations in the markers of hepatotoxicity and oxidative stress, resulting in the reversal of most of the parameters studied and were comparable to the standard hepatoprotective drug silymarin.     

Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.     

The modulatory influence of p-methoxycinnamic acid, an active rice bran phenolic acid, against 1,2-dimethylhydrazine-induced lipid peroxidation, antioxidant status and aberrant crypt foci in rat colon carcinogenesis

We investigated the chemopreventive effect of p-methoxycinnamic acid (p-MCA), an active phenolic acid of rice bran, turmeric, and Kaemperfia galanga against 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 consisted of control rats that received a modified pellet diet and 0.1% carboxymethyl cellulose. The rats in Group 2 received a modified pellet diet supplemented with p-MCA [80 mg/kg body weight (b.wt.) post-orally (p.o.)] everyday. The rats in Groups 3-6 received 1,2-dimethylhydrazine (DMH) (20 mg/kg b.wt.) via subcutaneous injections once a week for the first 4 weeks; additionally, the rats in Groups 4, 5 and 6 received p-MCA at doses of 20, 40 and 80 mg/kg b.wt./day p.o., respectively, everyday for 16 weeks. The rats were sacrificed at the end of the experimental period of 16 weeks. The DMH-treated rats exhibited an increased incidence of aberrant crypt foci (ACF) development; an increased crypt multiplicity; decreased concentrations of tissue lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lipid hydroperoxides (LOOH); decreased levels of tissue enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR); and decreased levels of non-enzymic antioxidants such as reduced glutathione (GSH) and vitamins C, E and A in the colon. Supplementation with p-MCA significantly reversed these changes and significantly inhibited the formation of ACF and its multiplicity. Thus, our findings demonstrate that p-MCA exerts a strong chemopreventive activity against 1,2-dimethylhydrazine-induced colon carcinogenesis by virtue of its ability to prevent the alterations in DMH-induced circulatory and tissue oxidative stress and preneoplastic changes. p-MCA was more effective when administered at a dose of 40 mg/kg b.wt. than at the other two doses tested.     

Hepatoprotective activity of bacoside A against <Emphasis Type="Italic">N</Emphasis>-nitrosodiethylamine-induced liver toxicity in adult rats

N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and γ-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.     

Hesperidin, a flavanone glycoside, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats

Myocardial infarction continues to be a leading cause of mortality world-wide. Novel therapies are needed to treat the myocardial ischemia. This study was undertaken to evaluate the cardioprotective role of hesperidin on isoproterenol-induced myocardial ischemia in rats. Myocardial ischemia was induced by subcutaneous injection of isoproterenol hydrochloride (85 mg/kg body weight), for two consecutive days. Isoproterenol-administered rats showed elevated levels of cardiac markers (aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, cardiac troponins T and I) when compared with control and hesperidin treatment groups (100, 200 and 400 mg/kg body weight). The serum levels of cardiac markers were significantly reduced at the doses of 200 mg and 400 mg. All further experiments were carried out at the 200 mg dose. Lipid peroxidation markers (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes) were elevated significantly in the plasma and heart whereas non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) were decreased significantly. Activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase declined significantly in the heart of ischemic rats. However, after hesperidin treatment, all the above parameters reverted to normal levels. This study demonstrated that the cardioprotective effect of hesperidin on ischemic rats could be due to its anti-lipid peroxidative and antioxidant properties.