Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats

The effect of aminoguanidine (AG) on nephrotoxicity induced by cisplatin (CDDP) was investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced nephrotoxicity, manifested biochemically by a significant elevation in serum urea, creatinine and a severe decrease in serum albumin. Moreover, marked increases in kidney weight, urine volume and urinary excretion of albumin were observed. Nephrotoxicity was further confirmed by a significant decrease in glutathione-S-transferase (GST, E.C. 2.5.1.18), glutathione peroxidase (GSH-Px, E.C. 1.11.1.9) and catalase (E.C. 1.11.1.6) and a significant increase in lipid peroxides measured as malondialdhyde (MDA) in kidney homogenates. Administration of AG (100 mg/kg per day p.o.) in drinking water 5 days before and 5 days after CDDP injection produced a significant protection against nephrotoxicity induced by CDDP. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, AG tended to normalize decreased levels of serum albumin. Urine volume, urinary excretions of albumin and GST and kidney weight were significantly decreased. Moreover, AG prevented the rise of MDA and the reduction of GST and GSH-Px activities in the kidney. These results suggest that AG has a protective effect on nephrotoxicity induced by CDDP and it may therefore improve the therapeutic index of CDDP.     

Protective effect of proanthocyanidins against doxorubicin‐induced nephrotoxicity in rats

Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The present study aimed to assess the protective effect of proanthocyanidins (PAs) against DOX‐induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg, i.v.) significantly increased kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of malondialdehyde, nitric oxide, cyclooxygenase‐2, and caspase‐3 activity with significant reduction in final body weight, serum albumin, kidney contents of reduced glutathione (GSH), and superoxide dismutase activity as compared with control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days before DOX and for 7 days after DOX ameliorated kidney function and oxidative stress parameters. Histopathological evidence confirmed the protective effects of PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi‐nephroprotective effect that might be attributed to its antioxidant, anti‐inflammatory, and antiapoptoic activities.     

Protective effect of Pongamia pinnata flowers against cisplatin and gentamicin induced nephrotoxicity in rats

Ethanolic extract of flowers of Pongamia pinnata was studied for its protective effect against cisplatin and gentamicin induced renal injury in rats. When the extract (300 & 600 mg kg(-1)) was administered orally for 10 days following cisplatin (5 mg kg(-1) i.p.) on day 5, toxicity of cisplatin, as measured by loss of body weight, elevated blood urea and serum creatinine declined significantly. Similarly in gentamicin (40 mg kg(-1) s.c.) induced renal injury, the extract (600 mg kg(-1)) normalized the raised blood urea and serum creatinine levels. Reversal of cisplatin and gentamicin renal cell damage as induced by tubular necrosis ie, marked congestion of the glomeruli with glomerular atrophy, degeneration of tubular epithelial cells with casts in the tubular lumen and infiltration of inflammatory cells in the interstitium was confirmed on histopathological examination. In the preventive regimen, co-administration of the extract with gentamicin significantly prevented the renal injury both functionally and histologically. Ethanolic extract of flowers had a marked nitric oxide free radical scavenging effect, suggesting an antioxidative property. Two flavonoids, known for their antioxidant activity viz. kaempferol and 3, 5, 6, 7, 8-pentamethoxy flavone were isolated from the extract. The results suggested that the flowers of Pongamia pinnata had a protective effect against cisplatin and gentamicin induced renal injury through antioxidant property.     

Protective effect of cannabidiol against cadmium hepatotoxicity in rats

The protective effect of cannabidiol, the non-psychoactive component of Cannabis sativa, against liver toxicity induced by a single dose of cadmium chloride (6.5 mg kg^?1 i.p.) was investigated in rats. Cannabidiol treatment (5 mg kg^?1/day, i.p.) was applied for five days starting three days before cadmium administration. Cannabidiol significantly reduced serum alanine aminotransferase, and suppressed hepatic lipid peroxidation, prevented the depletion of reduced glutathione and nitric oxide, and catalase activity, and attenuated the elevation of cadmium level in the liver tissue resulted from cadmium administration. Histopathological examination showed that cadmium-induced liver tissue injury was ameliorated by cannabidiol treatment. Immunohistochemical analysis revealed that cannabidiol significantly decreased the cadmium-induced expression of tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, caspase-3, and caspase-9, and increased the expression of endothelial nitric oxide synthase in liver tissue. It was concluded that cannabidiol may represent a potential option to protect the liver tissue from the detrimental effects of cadmium toxicity.     

Hepatoprotective effect of Origanum vulgare in Wistar rats against carbon tetrachloride-induced hepatotoxicity

The effect of an aqueous extract of Origanum vulgare (OV) leaves extract on CCl₄-induced hepatotoxicity was investigated in normal and hepatotoxic rats. To evaluate the hepatoprotective activity of OV, rats were divided into six groups: control group, O. vulgare group, carbon tetrachloride (CCl₄; 2 ml/kg body weight) group, and three treatment groups that received CCl₄ and OV at doses of 50, 100, 150 mg/kg body weight orally for 15 days. Alanine amino transferase (ALT), alkaline phosphatase (ALP), and aspartate amino transferase (AST) in serum, lipid peroxide (LPO), GST, CAT, SOD, GPx, GR, and GSH in liver tissue were estimated to assess liver function. CCl₄ administration led to pathological and biochemical evidence of liver injury as compared to controls. OV administration led to significant protection against CCl₄-induced hepatotoxicity in dose-dependent manner, maximum activity was found in CCl₄?+?OV3 (150 mg/kg body weight) groups and changes in the hepatocytes were confirmed through histopathological analysis of liver tissues. It was also associated with significantly lower serum ALT, ALP, and AST levels, higher GST, CAT, SOD, GPx, GR, and GSH level in liver tissue. The level of LPO also decreases significantly after the administration of OV leaves extract. The biochemical observations were supplemented with histopathological examination of rat liver sections. Thus, the study suggests O. vulgare showed protective activity against CCl₄-induced hepatotoxicity in Wistar rats and might be beneficial for the liver toxicity.     

Protective effect of resveratrol against pembrolizumab-induced hepatotoxicity and neurotoxicity in male rats

The present study investigates the effects of resveratrol (RSV) on brain and liver tissues in rats with pembrolizumab (PEMB)-induced toxicity. Obtained for the study were 28 male Sprague-Dawley rats (3–4 months old) which were divided into four groups: Group 1: Control. Group 2: Administered PEMB at 5 mg/kg/day i.p. for a week. Group 3: Administered RSV orally at the dose of 20 mg/kg/day for 30 days by gavage. Group 4: Administered PEMB and RSV at 20 and 5 mg/kg/day RSV, respectively, for 30 days. The results of this study revealed that PEMB leads to a significant increase in thiobarbituric acid reactive substance (TBARS) levels and a significant decrease in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) levels in the liver and brain tissues. The decreased SOD, CAT, GPx activities, and GSH levels increased significantly following RSV treatment in Group 4. The PEMB treatment showed histopathological alterations associated with strong positive cysteinyl aspartic acid-protease-3 (caspase-3) immunoreactivity, while RSV treatment reduced both the expression of caspase-3 protein and the histopathological changes. RSV administration prevents the biochemical, immunological, and histological alterations induced by PEMB. It can be suggested that the lower caspase-3 immunoreactivity in the PEMB + RSV group than in the PEMB group led to an inhibition of RSV on apoptosis.     

Protective effect of Trigonella foenum-graecum on thioacetamide induced hepatotoxicity in rats

Trigonella foenum-graecum belongs to the family Fabaceae and is indigenous to countries that lie on the eastern shores of the Mediterranean Sea and is also cultivated in India, Egypt and Africa. This study provides the evidence indicating the therapeutic effect of the extract prepared from the dried seeds of Trigonella foenum-graecum on an animal model of hepatotoxicity and on cell proliferation. Rats were induced liver cirrhosis by thioacetamide (0.03% in water for 16 weeks). Transmission electron microscopy of the liver tissue was done to evaluate liver cirrhosis. The herbal extract was administered orally for 3 weeks after induction and biochemical estimations were done. After the administration of extract the oxidative stress and lipid peroxidation were reversed. The elevated levels of alkaline phosphatase, γ-glutamyl transferase and selected biochemical markers of liver cirrhosis including drug metabolizing enzymes were also reversed. The study has implications in finding a treatment for liver cirrhosis by a natural herbal drug with no side effects.     

Toxicity of polycyclic aromatic hydrocarbons. V. Protective effect of beta-naphthoflavone against hepatotoxicity induced by diphenaldehyde in rats

Male Sprague-Dawley rats were treated ip with beta-naphthoflavone (40 mg/kg/day) in corn oil or in DMSO for three days. Diphenaldehyde (90 mg/kg in DMSO) was injected ip 24 hr after pretreatment. The increase in the levels of aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase, gamma glutamyl transpeptidase, and lactate dehydrogenase was significantly lower in rats pretreated with BNF. This suggests that the BNF-induced P-450 isozyme systems have a protective effect against the acute hepatotoxicity of diphenaldehyde.     

Protective effect of diosmin against doxorubicin-induced nephrotoxicity

Doxorubicin (Dox) is an anthracycline antibiotic that is primarily used for treating various solid tumors including that of pulmonary, ovary, breast, uterine, cervix, and several blood cancers. However, nephrotoxicity associated with Dox treatment limits its clinical use. Administration of Dox in combination with compounds exhibiting antioxidant properties are being used to minimize the side effects of Dox. Diosmin is a flavonoid glycoside with numerous beneficial properties that is found in the pericarp of many citrus fruits. Diosmin has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effects in response to various insults, although the exact mechanism remains unknown. Therefore, this study was designed to evaluate the effect of diosmin in preventing kidney damage in response to Dox treatment. Male Wistar rats were randomly divided into four groups: control group, Dox group (20 mg/kg, i.p.), Dox plus low-dose diosmin group (100 mg/kg orally), and Dox plus high-dose diosmin group (200 mg/kg orally). A single intraperitoneal injection of Dox resulted in kidney damage as evidenced by significant alterations in kidney markers, histological abnormalities, and the attenuation of antioxidant defense mechanisms (GSH, SOD, and CAT). Moreover, Dox treatment significantly altered the expression of oxidative stress, inflammatory, and anti-apoptotic protein markers. Diosmin pretreatment alleviated Dox-induced nephrotoxicity by ameliorating the antioxidant mechanism, decreasing inflammation and apoptosis, and restoring kidney architecture. In conclusion, our results indicate that diosmin is a promising therapeutic agent for the prevention of nephrotoxicity associated with DOX.     

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats

The widespread use of sodium nitrite (NaNO₂) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO ₂ is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO ₂-induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO ₂ at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO ₂ induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO ₂-treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO ₂-induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.     

Protective effect of Abutilon indicum against lead-induced reproductive toxicity in male Wistar rats

Despite ample literature on the toxic impact of lead on the environment and health, the exact mechanism of pathogenesis/toxicity is not clearly known. Because it is well established that lead induces oxidative stress, it is assumed that exposure to antioxidants may reduce the toxic impact of lead. In this study, we evaluated the impact of coadministration of the methanolic root extract of a plant Abutilon indicum (50, 100, 200 mg kg ⁻¹b.wt.) in mitigating the toxic impact of lead on the reproductive system of rats. In brief, Wistar rats were exposed to lead acetate in drinking water with or without coadministration of plant root extract and compared with that of control animals. After 45 days of exposure as outlined above, the animals were killed and the reproductive toxicity was assessed by sperm parameters, hormone and antioxidant enzyme assays, and testis histopathology. Significant reduction in testis weight, sperm count, testosterone levels, and antioxidant enzymes levels such as Superoxide Dismutase, Catalase, and Glutathione peroxidase was seen in lead-treated animals, confirming the toxic impact. The coadministration of A. Indicum (100 and 200 mg kg ⁻¹b.wt.) was found to bring the studied parameters close to the levels seen in untreated (control) animals. Our findings are indicative of the protective nature of A. Indicum against lead-induced reproductive toxicity in a dose-dependent manner. However, further characterization of the root extract is required to elucidate the probable mechanism of protection.     

Prophylactic effect of vitamin E against hepatotoxicity,nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

Considering that the involvement of reactive oxygen species （ROS） has been implicated in the toxicity of various pesticides, this study was designed to study the ameliorative effect of Vitamin E （100 mg/kg body weight） on mice （25 -30 mg） treated with diazinon （32.5 or 16.25 mg/kg body weight） organophosphate insecticide for 14 days. Subehronic DZN exposure and the protective effects of vitamins E （vitE） were evaluated for their effects on haematological indices, the enzymes concerning liver damage [plasma alanine aminotransferase （ ALT）, aspartate aminotaransferase （ AST）, alkaline phosphatise （ ALP）, and some parameters of kidney function （urea and creatinine） in mice. Additionally, the histopathological changes in liver and kidney tissue were examined. The high dose of diazinon （DZNH） decreased the body weight significantly at the end of experiment. Additionally, the liver and kidney were examines for histopathological changes. The high dose of diazinon decreased body weight significandy. Moreover, there was a statistically significant decrease in haemoglobin （Hb）, red blood cell （RBC） and hematocrit （Hct） in diazinon-treated mice compared to controls. This decrease was partially remedied in the diazinon-treated group that also received vitE. Damage in the liver and kidney tissues was also evident as elevated plasma ALT, AST, ALP, urea and creatinine. VitE partially counteracts the toxic effect of DZN and repairs tissue damage in the liver and kidney, especially when supplemented to 1/4 LD50 intoxicated animals. Histopathological changes in liver and kidney were observed only in 32.5 mg/kg DZN given group. These results suggest that the effects of DZN are dose dependent. No pathological findings were observed in vitE ＋ DZNtreated groups. According to the present study, we conclude that vitE ean reduce the detrimental impacts of diazinon on haematological indicies, as well as liver and kidney function [ Current Zoology 55 （3） ： 219 - 226, 2009].     

Prophylactic effect of vitamin E against hepatotoxicity,nephrotoxicity, haematological indices and histopathology induced by diazinon insecticide in mice

Considering that the involvement of reactive oxygen species(ROS)has been implicated in the toxicity of various pesticides,this study was designed to study the ameliorative effect of Vitamin E(100 mg/kg body weight)on mice(25-30 mg)treated with diazinon(32.5 or 16.25 mg/kg body weight)organophosphate insecticide for 14 days.Subchronic DZN exposure and the protective effects of vitamins E(vitE)were evaluated for their effects on haematological indices,the enzymes concerning liver damage [plasma alanine aminot...     

Protective effect of cyclic AMP against cisplatin-induced nephrotoxicity

We reported earlier that reactive oxygen species are implicated in necrotic injury induced by a transient exposure of cultured renal tubular cells to a high concentration of cisplatin but not in apoptosis occurring after continuous exposure to a low concentration of cisplatin. We report here the protective effect of cyclic AMP against cisplatin-induced necrosis in cultured renal tubular cells as well as cisplatin-induced acute renal failure in rats. Several pharmacological agents that stimulate cyclic AMP signaling, including the nonhydrolyzable cyclic AMP analogue dibutyryl cyclic AMP, forskolin, 3-isobutyl-1-methylxanthine, and a prostacyclin analogue, beraprost, prevented cisplatin-induced cell injury in a protein kinase A-dependent manner. Cisplatin enhanced lipid peroxidation, decreased CuZn superoxide dismutase (SOD) while enhancing MnSOD activity, and increased cellular tumor necrosis factor-alpha (TNF-alpha) content. The elevation of TNF-alpha content and cell injury induced by cisplatin were attenuated by p38 mitogen-activated protein kinase (MAPK) inhibitors including SB203580 and PD169316. Indeed, cisplatin increased the number of phosphorylated p38 MAPK-like immunoreactive cells. These intracellular events were all reversed by antioxidants such as N-acetylcysteine (NAC) and glutathione or cyclic AMP analogues. The in vivo acute renal injury after cisplatin injection was associated with the elevation of renal TNF-alpha content. The cisplatin-induced renal injury and the increase in TNF-alpha content were reversed by NAC or beraprost. These findings suggest that cyclic AMP protects renal tubular cells against cisplatin-induced oxidative injury by obliterating reactive oxygen species and subsequent inhibition of TNF-alpha synthesis through blockade of p38 MAPK activation.     

Protective effect of pinitol against D-galactosamine-induced hepatotoxicity in rats fed on a high-fat diet

The protective effect of pinitol against D-galactosamine (GalN)-induced liver damage was examined. Forty male Sprague-Dawley rats were divided into normal control, GalN control, and pinitol groups (0.5%, 1%, and 2%). After 8 weeks of feeding, a single dose of GalN (650 mg/kg) was administered 24 h before their sacrifice. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly increased after an injection with GalN (P<0.05), but pinitol supplementation at the level of 0.5% reversed these changes to normal levels. Significant decreases in serum triglyceride and cholesterol and increases in hepatic cholesterol were observed in GalN-intoxicated rats. However, supplementation with pinitol significantly attenuated these trends. In addition, pinitol elevated the Mn-superoxide dismutase, glutathione reductase, and catalase activities, prevented hepatic lipid peroxidation, and restored the hepatic GSH levels and cytochrome P450 2E1 function. Thus, 0.5% pinitol supplementation protected the rats from the hepatotoxicity induced by GalN, at least part of its effect being attributable to attenuation of the oxidative stress and inflammatory process promoted by GalN.     

Protective effect of Nasturtium officinale R. Br and quercetin against cyclophosphamide-induced hepatotoxicity in rats

Molecular Biology Reports - Cyclophosphamide (CPA) is used in the management of autoimmune conditions and malignant illnesses. However, its therapeutic use is limited because of its severe side...     

Protective role of zinc in nickel induced hepatotoxicity in rats

This study was planned to determine the protective role of zinc, if any, in attenuating the toxicity induced by nickel sulfate in rat liver. Female Sprague Dawley (SD) rats received either nickel alone in the dose of 800 mg/l in drinking water, zinc alone in the dose of 227 mg/l in drinking water, and nickel plus zinc or drinking water alone for a total duration of eight weeks. The effects of different treatments were studied on various parameters in rat liver which include antioxidant enzymes, levels of nickel and zinc and histoarchitecture at the light microscopic level. Further, the activities of hepatic marker enzymes AST and ALT were also studied in rat serum. Nickel treatment to the normal control animals, resulted in a significant increase in lipid peroxidation and enzyme activities of catalase and glutathione-S-transferase. On the contrary, nickel treatment to normal rats caused a significant inhibition in the levels of reduced glutathione. Superoxide dismutase activity was found to be decreased which however was not significant. Interestingly, when Zn was supplemented to nickel treated rats, the activities of catalase, and glutathione-S-transferase and the levels of GSH and lipid peroxidation came back to within normal limits. Activities of serum AST and ALT were increased significantly following nickel treatment to normal rats. Simultaneous zinc administration to nickel treated rats tended to restore the altered levels of AST and ALT. Normal control and zinc treated animals revealed normal histology of liver. On the other hand, nickel treated animals showed alterations in normal hepatic histoarchitecture which comprise of vacuolization of the hepatocytes and dilatation of sinusoids as well as increase in the number of bi-nucleated cells. Administration of zinc to nickel treated rats resulted in marked improvement in the structure of hepatocytes, thus emphasizing the protective potential of zinc in restoring the altered hepatic histoarchitecture. The nickel administration to normal rats indicated increased concentrations of nickel and decreased concentrations of zinc. However, zinc effectively brought the altered levels of nickel and zinc to within normal range. The study concludes that zinc has the potential in alleviating the toxic effects of nickel in rat liver because of its property to induce metallothionein (S-rich protein) as a free radical scavenger, or its indirect action in reducing the levels of oxygen reactive species.     

Protective effects of melatonin against carbon tetrachloride hepatotoxicity in rats

Melatonin is an indolamine, mainly secreted by the pineal gland into the blood of mammalian species. The potential for protective effects of melatonin on carbon tetrachloride (CCl(4))-induced acute liver injury in rats was investigated in this work. CCl(4) exerts its toxic effects by generation of free radicals; it was intragastrically administered to male Wistar rats (4 g kg(-1) body weight) at 20 h before the animals were decapitated. Melatonin (15 mg kg(-1) body weight) was administered intraperitoneally three times: 30 min before and at 2 and 4 h after CCl(4) injection. Rats injected with CCl(4) alone showed significant lipid and hydropic dystrophy of the liver, massive necrosis of hepatocytes, marked increases in free and conjugated bilirubin levels, elevation of hepatic enzymes (alanine aminotransferase and aspartate aminotransferase) in plasma, as well as NO accumulation in liver and in blood. Melatonin administered at a pharmacological dose diminished the toxic effects of CCl(4). Thus it decreased both the structural and functional injury of hepatocytes and clearly exerted hepatoprotective effects. Melatonin administration also reduced CCl(4)-induced NO generation. These findings suggest that the effect of melatonin on CCl(4)-induced acute liver injury depends on the antioxidant action of melatonin.