Protective effects of melatonin against carbon tetrachloride-induced hepatotoxicity in rats: a light microscopic and biochemical study

The aim of this study was to examine the protective effects of melatonin against CCl4-induced hepatotoxicity in the rat. Twenty-four male Wistar rats were divided into three groups. Group I was used as a control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and melatonin for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and conjugated bilirubin levels were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All serum biochemical parameters were significantly higher in animals treated with CCl4 than in the controls. When rats injected with CCl4 were treated with melatonin, significantly reduced elevations in serum biochemical parameters were found. In liver sections of the CCl4-injected group, necrosis, fibrosis, mononuclear cell infiltration, haemorrhage, fatty degeneration and formation of regenerative nodules were observed. Additionally, apoptotic figures, microvesicular steatosis and hydropic degeneration in hepatocytes were seen in this group. In contrast, the histopathological changes observed after administration of CCl4 were lost from rats treated with CCl4 and melatonin. Except for mild hydropic degeneration of the hepatocytes, a normal lobular appearance was seen in the livers of this group. The results of our study indicate that melatonin treatment prevents CCl4-induced liver damage in rats.     

Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats

Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson’s trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.     

Modulation of DMBA-induced biochemical changes by organoselenium compounds in blood of rats

The protective role of two synthetic organoselenium compounds 1-isopropyl-3-methylbenzimidazole-2-selenone (SeI) and 1, 3-di-p-methoxybenzylpyrimidine-2-selenone (Sell) was examined against the 7,12-dimethylbenz[a]anthracene (DMBA)-induced changes in biochemical parameters in blood of rats. Albino Winstar rats (150-200 g body wt) were treated with single dose of DMBA (50 mg/kg body wt) and organoselenium compounds (25 micromol/kg) for 4 weeks at two days internal. Blood was taken from the anaesthetized rats ventricle from their hearts for biochemical analysis. Administration of DMBA resulted in elevation of urea, uric acid and creatinine levels as well as AST, ALT and LDH activities and decrease in levels of total proteins, albumin and globulin. SeI and SeII caused a significant (p<0.05) decrease in urea, uric acid and creatinine levels and alanine aminotransferase (ALT); aspartate aminotransferase; (AST) and lactate dehydrogenase (LDH) activities and significantly increased the levels of total protein and albumin (p<0.05). These organoselenium compounds are likely to be beneficial in human health.     

Effects of Ballota nigra on blood biochemical parameters and insulin in albino rats

Ingestion of aqueous 70% ethanol extract of Ballota nigra (400 mg/kg body weight for 7 days) by albino rats (n=10) was investigated to study its effects on glucose, total cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), troponin I (TnI), serum creatine kinase (CK), total protein, total bilirubin and blood urea. Ballota nigra extract caused a significant decrease in blood glucose, total serum cholesterol and CK levels. Blood levels of TnI, AST, ALT, triglycerides, total bilirubin, total protein and blood urea were unchanged. The hypoglycemic effect of Ballota nigra extract on albino rats was further investigated by conducting a glucose tolerance test intraperitoneally (IPGTT). Healthy rats that were fasting for 18 hours followed by administration of a dose of 400 mg/kg body weight of the crude extract of Ballota nigra, orally. A significant decrease in blood glucose levels (after 15, 30, and 45 minutes) with a significant increase in serum insulin level (after 15 and 30 minute) was noted. These results suggest that, the crude extract of Ballota nigra have hypoglycemic, insulin-releasing and cholesterol lowering effects in rats.     

Biochemical predictors for Sars-Cov-2 severity

It is of interest to assess the inflammatory marker profile in SARS-CoV-2 patients and to correlate the levels of systemic inflammatory biomarkers such as neutrophil-to-lymphocyte ratio (NLR), C-Reactive Protein CRP, Ferritin, Creatine kinase (CK), Lactate dehydrogenase (LDH) and liver function analytes total serum proteins, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with the severity of SARS-CoV-2 infections. A total of 1000 COVID-19 positive patient''s data were collected. Laboratory assessments consisted of NLR (neutrophil-lymphocyte ratio) by cell counter, C Reactive Protein (CRP) by immunoturbidimetry, Ferritin by electrochemiluminescence (ECLIA) and Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total Bilirubin, Direct Bilirubin, Total Protein and Albumin by spectrophotometry. The mean plasma CRP levels, NLR, ferritin, CK and LDH levels were higher in severe cases than in non-severe cases, and the difference was statistically significant (p<0.05). All liver function tests such as the total and direct bilirubin, AST, ALT, ALP, total protein and albumin were higher in severe patients than non-severe patients and the difference was statistically significant (p<0.05). Data indicate that NLR, CRP, Ferritin, CK, LDH and liver function analytes have a crucial role as prognostic markers for SARS-CoV-2 infections and hence should be routinely recommended for risk assessment and stratification of the patients to reduce the associated morbidity and mortality.     

Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats.     

Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats

Vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetine on the acute hepatic injury caused in the rat by the administration of CCl4 in vivo. Vinpocetine (2.1, 4.2, 8.4 mg/kg) or silymarin (30 mg/kg) was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl4-treated rats decreased the elevated alanine aminotransferase (ALT) by 49.3, 58.1 and 63.6%, aspartate aminotransferase (AST) by 10.5, 22.6 and 27.2% and alkaline phosphatase (ALP) by 52.5, 59.6 and 64.9%, respectively, and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin-treated rats compared with vehicle-treated CCl4-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 82.6% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats reduced liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects.     

In vitro and in vivo hepatoprotective activity of Cissampelos pareira against carbon-tetrachloride induced hepatic damage

Administration of hydroalcoholic extract of Cissampelos pareira roots (CPRE) and standard drug silymarin in rats showed significant hepatoprotective action against CCl4 induced hepatotoxicity. Elevated serum marker enzymes of AST, ALT, ALP and serum bilirubin were significantly reduced to near normal level in CPRE treated rats. Lipid peroxidation level was decreased significantly in CPRE 100, 200, 400 mg/kg doses treatment groups. In case of antioxidant enzymes SOD, catalase levels were increased significantly after CPRE 200, 400 mg/kg doses, similarly it increased the enzyme levels of GST, GPx, and GSH. CPRE 200, 400 mg/kg decreased cholesterol level, and increased triglyceride level. In vitro hepatoprotective activity of the extract was evaluated at 20, 40, 60, 80 and 100 microg/ml concentration against CCl4 (1%) induced toxicity in freshly isolated rat hepatocytes. HepG2 cells showed significant dose dependent increase in percentage viability at the doses 20, 40, 60, 80 and 100 microg/ml of CPRE compared to CCl4 exposed HepG2 cells. Results of this study strongly demonstrate Cissampelos pariera having good hepatoprotective potential.     

Effects of Selenium and Vitamin E,in Addıtıon to Melatonin,Against Oxidative Stress Caused by Cadmium in Rats

The present study was carried to evaluate the protective effects of melatonin alone and vitamin E with selenium combination against high dose cadmium-induced oxidative stress in rats. The control group received subcutanous physiological saline. The first study group administered cadmium chloride (CdCl₂) by subcutaneous injection of dose of 1 mg/kg. The second study group administered cadmium plus vitamin E with selenium (1 mg/kg sodium selenite with 60 mg/kg vitamin E); the third study group administered cadmium plus 10 mg/kg melatonin (MLT); the fourth study group administered CdCl₂ plus a combination of melatonin in addition to vitamin E and selenium for a month. Determination levels of plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), blood superoxide dismutase (SOD), creatinine alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and urea were measured in serum. In only CdCl₂ administered group, the MDA, creatinine, ALT, AST, ALP, and urea levels in the serum were significantly higher than the control group (p < 0.05). Whereas in all other groups, this values were significantly lower than the only CdCl₂ administered group (p < 0.05). Erythrocytes GSH-Px, serum SOD activities of only CdCl₂ received group were significantly lower than the control group (p < 0.05). In conclusion, vitamin E + Se, melatonin and vitamin E, and Se, in addition to MLT combinations, had protective effects against high dose cadmium-induced oxidative damage.     

Gender and age-specific reference intervals of common biochemical analytes in Chinese population: Derivation using real laboratory data

BackgroundIndirect sampling methods are not only inexpensive but also efficient for establishing reference intervals (RIs) using clinical data. This study was conducted to select fully normal records to establish ageand gender-specific RIs for common biochemical analytes by laboratory data mining.MethodsIn total, 280,206 records from 2014 to 2018 were obtained from Peking Union Medical College Hospital. Common biochemical analytes total protein, albumin, total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT), glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), potassium, sodium, chlorine, calcium, urea, glucose, uric acid (UA), inorganic phosphorus, creatinine (Cr), total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol] were measured using an automatic analyzer. Sources of variation were identified by multiple regression analysis. The 2.5th and 97.5th percentiles were calculated as the lower and upper limits of the RIs, respectivelyResultsGender was the major source of variation among the 13 common biochemical analytes with an rp > 0.15. In contrast to the value listed in the WS/T 404, nearly all RIs established in this study were significantly narrower. Furthermore, age-specific RIs should be determined for DBil, LDH, and urea, whereas gender-specific RIs are suggested for GGT, LDH, and urea.ConclusionsWe recommend that gender-specific RIs should be established for ALT, AST, GGT, DBil, TBil, UA, and Cr as well as genderand age-specific RIs for urea and ALP. Through indirect sampling, ageand gender-specific RIs for common biochemical analytes were established and analyzed.     

Blueberry extract attenuates γ-radiation-induced hepatocyte damage by modulating oxidative stress and suppressing NF-κB in male rats

Radiation exposure is known to produce many harmful effects in biological systems, and these effects are often mediated by oxygen free radicals. Because blueberries are rich in antioxidant compounds such as anthocyanins and phenolic acids, we divided forty adult rats into four treatment groups of 10 (G1–4) as follows: G1 rats were used as a control, G2 rats were irradiated with 8?Gy at 2?Gy/week at a dose rate of 0.5?Gy/min, G3 rats were administered blueberry extract (200?mg/kg) and G4 rats were administered blueberry extract during the same irradiation period. In subsequent determinations, γ-irradiated rats had increased levels of cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL), and significantly elevated liver enzyme activities, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and total bilirubin. In contrast, significant reductions in albumin, total protein and globulin were observed, whereas gamma irradiation decreased activities of the antioxidant enzymes glutathione (GSH), catalase (CAT), xanthine dehydrogenase (XDH) and superoxide dismutase (SOD). We also observed incremental increases in DNA fragmentation percentages and histopathological changes in liver tissues. Serum pro-inflammatory cytokine levels (IL-6, IL-10 and TNF-α) were significantly elevated and hepatic NF-кB was upregulated. In G4 rats, treatments with blueberry extract restored liver pro-oxidant status, reduced cytokine levels, ameliorated histopathological parameters and reduced DNA damage. In conclusion, γ-radiation exerts toxic effects in the rat livers, and blueberry extract is protective against these.     

Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats

This study was conducted to explore possible protective effect ofCnidoscolus aconitifolius (CA) leaf extract on carbon tetrachloride (CCl4)-induced hepatotoxicity and haemotoxicity in experimental animal models. Thirty six rats of six per group were used in this study. Group I received 10ml/kg normal saline as control. Group II-VI rats were administered with 1.25ml/kg body weight (bwt) of carbon tetrachloride intraperitonealy. Animals in groups III, IV, V and VI were however pre-treated with aqueous extract of Cnidoscolus aconitifolius at 100, 250, 500 and 750mg/kg body weight (bwt) respectively. Administration of CCL4 in untreated rats led to microcytic hypochromic anaemia, thrombocytopenia, increased erythrocyte fragility and stress induced leucocytosis accompanied with significant increase in neutrophils and decrease in lymphocyte counts. CCl4 also led to significant increase in serum transaminases (ALT and AST) and phosphatase (ALP) respectively compared with control animals. Also, CCL4 produced significant increase in serum blood urea nitrogen (BUN) and creatinine compared with normal rats. Pre-treatment with Cnidoscolus aconitifolius leaf extract brought about significant restoration of the haematological parameters to values that were comparable to those of the control with concomitant decrease in the activities of the marker of hepatic damage enzymes (ALT, AST and ALP), in a dose-dependent manner. Similarly, serum levels of blood urea nitrogen (BUN) and creatinine were also brought to near normal by the CA in a dose-dependent manner. From this study, we conclude that pre-exposure to Cnidoscolus aconitifolius leaf extract considerably reduced the effect of CCl4 on the blood parameters and ameliorated hepatic damage by the haloalkane. Keywords: Hepatotoxicity, Haemotoxicity, Carbon tetrachloride, Cnidoscolus aconitifolius, Rats.     

Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats

The hepatoprotective and antioxidant effect of Cassia fistula Linn. leaf extract on liver injury induced by diethylnitrosamine (DEN) was investigated. Wistar rats weighing 200+/-10g were administered a single dose of DEN (200mg/kg b.w., i.p.) and left for 30 days. For hepatoprotective studies, ethanolic leaf extract (ELE) of C. fistula Linn. (500mg/kg b.w., p.o.) was administered daily for 30 days. AST, ALT, ALP, LDH, gamma-GT and bilirubin were estimated in serum and liver tissue. Lipid peroxidation (LPO), SOD and CAT were also estimated in liver tissue as markers of oxidative stress. DEN induced hepatotoxicity in all the treated animals were evident by elevated serum ALT, AST, ALP and bilirubin levels and a simultaneous fall in their levels in the liver tissue after 30 days. Induction of oxidative stress in the liver was evidenced by increased LPO and fall in the activities of SOD and CAT. ELE administration for 30 days prevented the DEN induced hepatic injury and oxidative stress. In conclusion, it was observed that ELE of C. fistula Linn. protects the liver against DEN induced hepatic injury in rats.     

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats

It has been proposed carbon tetrachloride (CCl₄) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl₄-induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl₄ (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl₄ significantly inhibited alterations in the serum levels of AST, ALP (^**P < 0.01), and ALT (^***P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl₄-induced hepatotoxicity in rats.     

Serum constituents of Suncus murinus

Blood samples were collected by cardiac puncture from nine-week-old suncus, mice and rats those had been fasted for 16 hours, and the serum was assayed for the levels of corticosterone, cortisol, and other constituents. The following results were obtained: The serum levels of corticosterone and cortisol and corticosterone/cortisol ratio of suncus were about the same as those of human. The SGPT, gamma-GT, ALP, LDH, Ca and K values in suncus were all within the normal range of the respective values in human. SGOT, amylase, BUN, Na, Cl, Fe and inorganic phosphate values were higher, and total cholesterol, triglyceride, phospholipid, creatinine, urea, total protein, albumin and bilirubin levels were lower in suncus than the respective normal values in human. The values of SGOT, amylase, ZTT, and K were higher in female than in male suncus, while the values of gamma-GT and ALP were higher in the male. Feeding the animals individually in the individual cages for a week increased the values of direct bilirubin, total cholesterol, ZTT, Na, K and Cl and lowered the value of urea. The values of SGPT, ALP and triglyceride of suncus obtained in 1984 were higher, the value of albumin was lower, than the respective values obtained in 1983. The value of cholinesterase in suncus was very small.     

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.     

Anti-inflammatory effects and hepatotoxicity of Tripterygium-loaded solid lipid nanoparticles on adjuvant-induced arthritis in rats

Tripterygium wilfordii Hook f. (TWHF) has been demonstrated to have anti-inflammatory, immunosuppressive effects and its clinical use was restricted to some extent due to some toxic effects on the digestive, urogenital, and blood circulatory systems, especially the male reproductive system. In the previous study, we had confirmed that TWHF-loaded solid lipid nanoparticles (SLN) have protective effects on male reproductive toxicity in rats. Anti-inflammatory effects and hepatotoxicity of TWHF-SLN remain to be unidentified. The present study was focused on the anti-inflammatory effect of complete Freund's adjuvant-induced arthritis in rats treated with TWHF-SLN as well as the effects of SLN delivery system on decreasing the hepatotoxicity induced by tripterygium. Sixty-four healthy male rats were randomly divided into eight groups with eight rats each. From day 18 after FCA injection, TWHF-SLN group (120, 60, 30mg/kg) and TWHF group (120, 60, 30mg/kg) were administered by oral gavage for 24 consecutive days. The control group was with saline and model control group was without any treatment. The volume of the right hind paws was evaluated at 0, 4, 8, 12, 18, 24, 30, 36 and 42 days post-injection of FCA by a home-made connected device. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL) and albumin (ALB) levels were evaluated by an autoanalyzer. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) malondialdehyde (MDA) and xanthine oxidase (XOD) levels were determined using commercial kits. The PG level in sera was examined by double antibody sandwich method. Tissue histopathology was evaluated with hematoxylin and eosin (H&E). The results show that TWHF-SLN can significantly reduce rat paw volume at 60mg/kg (p<0.05) and PG levels in serum (p<0.05); the levels of ALT, AST, ALP, GGT in serum and MDA, XOD, GSH-PX in liver were not significantly elevated. Histopathology observation found that free TWHF caused more serious damage to the liver than TWHF-SLN. These results revealed that SLN delivery system can enhance the anti-inflammatory activity of TWHF, and meanwhile has a protective effect against TWHF-induced hepatotoxicity.     

Inhibition of carbon tetrachloride-induced lipid peroxidation by novel antioxidants in rat hepatic microsomes: dissociation from hepatoprotective effects in vivo

The ability of two novel antioxidants, U-74,006F and U-78,517G, as well as the known antioxidant N,N'-diphenyl-p-phenylenediamine to inhibit lipid peroxidation induced by carbon tetrachloride (CCl4) was investigated in Aroclor 1254-induced rat hepatic microsomes. All three compounds completely inhibited lipid peroxidation in microsomes as measured by the formation of thiobarbituric acid reactive substances (TBARS). Inhibition of lipid peroxidation was not a function of decreased bioactivation of CCl4, as the compounds did not substantially inhibit benzphetamine N-demethylase activity or covalent binding of [14-C]CCl4 to lipid or protein. Parallel studies examined the hepatoprotective effects of the compounds in vivo. Rats were pretreated with antioxidant or vehicle prior to administration of CCl4 (300 or 600 microL/kg i.p.). Sera were collected 24 h postadministration of CCl4 and analyzed for alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and total bilirubin. Administration of CCl4 produced elevations in ALT, moderate changes in bilirubin, and no change in ALP activities. Histological examination of CCl4-treated livers revealed lipidosis and centrilobular necrosis. The antioxidants partially improved the clinical chemistry parameters, but had minimal effects on the histological lesion. In contrast to the complete inhibition of lipid peroxidation observed in the in vitro studies, none of the antioxidants markedly protected against CCl4-induced toxicity in vivo.     

Reduction of carbon tetrachloride-induced nephropathy by melatonin administration

The aim of this study was to investigate possible protective effects of melatonin on carbon tetrachloride (CCl4)-induced renal damage in rats. A total of 24 animals were divided into three equal groups: the control rats received pure olive oil subcutaneously, rats in the second group were injected with CCl4 (0.5 ml kg-1, s.c. in olive oil) and rats in the third group were injected with CCl4 (0.5 ml kg-1) plus melatonin (25 mg kg-1, s.c. in 10% ethanol) every other day for 1 month. At the end of the experimental period, the animals were sacrificed and blood samples were collected. The kidneys were removed and weighed. Urea and creatinine levels were determined in blood samples. Histopathological examination of the kidney was performed using light microscopic methods. Administration of CCl4 significantly increased relative kidney weight (g per 100 g body weight) and decreased serum urea levels compared to controls (p<0.01). Melatonin treatment significantly (p<0.01) reduced relative kidney weight, and it produced a statistically equal (p=0.268) relative weight with the kidneys of control rats. CCl4 administration alone also caused histopathologically prominent damage in the kidney compared to the control group. Glomerular and tubular degeneration, interstitial mononuclear cell infiltration and fibrosis, vascular congestion around the tubules, and interstitial haemorrhage in perivascular areas were observed in the renal cortex and cortico-medullary border. However, the affect of CCl4 on the medulla was limited. Melatonin provided protection against CCl4-induced renal toxicity as was evident by histopathological evaluation. In view of the present findings, it is suggested that melatonin protects kidneys against CCl4 toxicity.