Protective effect of Clerodendrum colebrookianum leaves against iron-induced oxidative stress and hepatotoxicity in Swiss albino mice.

Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases.

Amoxycillin Clavulanic Acid Induced Hepatotoxicity.

Drug-related hepatotoxicity is a serious health problem, with broad implications for patients, healthcare providers, the pharmaceutical industry and governmental regulatory agencies. Herein we report a rare case of amoxycillinclavulanic acid combination induced liver injury of cholestatic pattern in 40 years old, well educated male patient. Patient gave history that though other drugs were given to him by his physician for fever with chills & rigors, malaise, bodyache, except amoxycillin-clavulanic acid combination all other drugs were well tolerated previously by the patient, without appearance of jaundice. So jaundice in this patient was most probably due to amoxycillinclavulanic acid combination. Though severe liver injury is rare, proper history should be taken while prescribing amoxycillin-clavulanic acid combination. Attention must be paid to potential side-effects of the drugs and close follow-up with patients is a medical necessity to evaluate adverse reactions, especially in case of amoxycillinclavulanic acid combination.

Azadirachta indica mitigates DMBA-induced hepatotoxicity: A biochemical and radiometric study.

The hepatoprotective potential of aqueous Azadirachta indica leaf extract (AAILE) was assessed against DMBA-induced hepatotoxicity. DMBA  (7,12-dimethylbenz[a] anthracene) treatment (40 mg/kg body weight, ip) to male Balb/c mice resulted in the derailment of liver function as revealed by extremely slow clearance of 99mTc-mebrofenin from liver, elevated levels of alkaline phosphatase (ALP) and alanine transaminase (ALT), compared to control group. In addition, elevated micronuclei score and high apoptotic index indicated hepatogenotoxicity in DMBA-treated mice. DMBA treatment also upregulated cytochrome P450 (CYP), cytochrome b5 (Cyt b5) and decreased glutathione-S-transferase activity in hepatic tissue, compared to control group. Enhanced lipid peroxidation (LPO) levels along with decreased reduced glutathione (GSH) level were also observed in DMBA group, compared to control group. AAILE co-treatment (200 mg/kg body weight, po, thrice a week) for 8 weeks followed by DMBA injection showed significant improvement in hepatic status, as revealed by normalization of 99mTc-mebrofenin clearance rate, decreased ALP and ALT levels, reduced genotoxicity in terms of micronuclei score and apoptotic index. Levels of LPO were significantly decreased along with increased hepatic GST and GSH levels in AAILE + DMBA group, compared to DMBA group. However, no significant change was observed in hepatic CYP and Cyt b5 levels, compared to DMBA group. The results indicated that AAILE effectively ameliorated DMBA-induced hepatotoxicity.

Liver Function Tests in Type 2 Diabetes Mellitus Patients with and without Oral Hypoglycemic Agents and Statin Intake.

Background: Type 2 diabetes (T2DM) is often associated with liver function abnormalities, covering the entire spectrum from asymptomatic transamnitis to cirrhosis. The oral drugs used in diabetes are also associated with hepatic insult. Aims: Here we have tried to assess the prevalence the liver function test abnormality in type 2 diabetes mellitus patients with special reference to intake of oral hypoglycemic agents (OHA) and statins. Methods: We selected 101 patients of Type 2 Diabetes mellitus (T2DM). Among those diabetic patients 50 were on oral hypoglycemic drugs (OHA) and statins for at least last 6 months. Another 51 age and sex matched patients were diabetic but not on these drugs. The patients were screened for any existing liver disease by biochemical tests. Results and analysis: Our results showed that the prevalence of elevated liver enzymes and bilirubin is more in Diabetic patient than normal values but the oral hypoglycemic drugs and statins had no added effect. Altogether 70 patients (69.3%) had at least one liver function test abnormality. In our study, 4.95% of the patients had elevated bilirubin (>2.5 mg/dL). 24.75% of the study patients had ALT levels above normal (40 U/L) although high values (>100 U/L) were present only in 5 (4.95%). High AST levels (>40) was found in 34.65% cases. Mean alkaline phosphatase levels in 2 groups were similar (213.96 ± 46.2 vs. 222.75 ± 42.52 U/ L). Serum proteins, INR and alkaline phosphatase did not also show any association with drug intake in our study. Conclusion: Thus screening for liver function abnormalities can be a useful test in diabetic population to prevent future complications.

Protective Effect of Ethyl Acetate Extract of Acacia Catechu in Carbon Tetrachloride Induced Hepatotoxicity.

Objective: To study the protective effect of ethyl acetate extract of Acacia catechu in carbon tetrachloride induced hepatotoxicity in albino rats. Methods: The liver damage in albino rat was induced by a subcutaneous injection of 50%v/ v carbon tetrachloride in olive oil at the dose of 2ml/kg twice a week for 14days. The hepatoprotective activity was monitored biochemically by estimating serum transaminases, serum alkaline phosphatase, serum bilirubin and serum protein after intraperitoneal injection of ethyl acetate extract of Katha(250mg/kg). Silymarin(5mg/kg.I.P) was given as a reference drug. The histopathological changes of liver samples were compared with that of control. Results: Ethyl acetate extract of Acacia catechu inhibited carbon tetrachloride induced liver toxicity in albino rats at 250mg/kg body weight as assessed by the biochemical and histological examination. Conclusion: Ethyl acetate extract of “Katha” exhibited significant hepatoprotective activity.

Assessment of the protective role of green tea on doxorubicin induced hepatic and renal injuries in albino rats

The present study has been undertaken to investigate the ameliorative effect of green tea [GT] on doxorubicin [Doxo]-induced hepatotoxicity and nephrotoxicity in albino rats. The harmful effects of Doxo on some antioxidant enzymes, catalase [CAT], superoxide dismutase [SOD] and glutathione-S-transferase [GST] were studied. Reduced glutathione [GSH] and malondialdehyde [MDA] in liver and kidney homogenates were investigated. Quantitative and qualitative extents of DNA damage in the liver cells were also estimated using Cornet assay. Thirty two male adult albino rats [180-200 g] were divided into four groups [n=8] as follows; [1] Control group: was orally administered 1 ml/rat of 0.5% carboxymethyl cellulose [CMC] in distilled water, [2] Doxo group: after 10 days, Doxo was administered a single i.p. dose of 15 mg/kg body weight, [3] GT group: rats received 100 mg/kg body weight, p.o. of GT for 10 days and [4] Doxo and GT group: rats received 100 mg/kg body weight, p.o. of GT for 10 days prior to Doxo administration as a single i.p. dose of 15 mg/kg body weight. Doxorubicin-induced significant increase in serum levels of AST, ALT and gamma-glutamyl transpeptidase [GGT] for liver and urea and creatinine for kidney which were decreased by pretreatment with GT. Total serum protein and albumin levels were decreased after treatment with Doxo but this effect was attenuated by pretreatment with GT. Catalase, SOD, GST activities and GSH content of liver and kidney were significantly elevated by pretreatment with GT compared to Doxo-treated rats. Doxorubicin significantly increased in MDA levels. DNA damage measured as tail length, tail DNA% and tail moment were increased after treatment of Doxo while pretreatment with GT improved this effect. This study suggests that green tea has potential protective effect against doxorubicin-induced hepatoxicity and nephrotoxicity. So, it may be worthy to consider the usefulness of GT as adjuvant therapy in cancer management

Therapeutic efficacy of alpha lipoic acid in combination with succimer against lead-induced oxidative stress, hepatotoxicity and nephrotoxicity in rats

Lead toxicity is a worldwide health problem due to continuous exposure of the population to lead in the environment especially workers in industries. It affects many body organs especially the liver and kidneys. The aim of this study is to investigate and compare the therapeutic potential of alpha lipoic acid [ALA] when it is administrated alone and in combination with succimer or dimercaptosuccinic acid [DMSA] against lead induced oxidative stress, hepatotoxicity and nephrotoxicity. Seventy five healthy male albino rats were used divided into 5 equal groups. Group [1] the control group was administrated distilled water orally for 6 weeks. Group [II] rats were given lead acetate [0.2%] in drinking water for 5 weeks and distilled water only orally during the 6[th] week. Group [III, IV and V] rats were given lead acetate [0.2%] in drinking water for 5 weeks followed by DMSA in a dose of 20 mg/kg body weigh/day intraperitoneally [i.p.] alone, ALA in a dose of 25 mg/kg body weigh/day [i.p.] alone and both drugs in combination during the 6[th] week only respectively. Rats were sacrificed after six weeks. Blood lead level serum lipid peroxides [TBARS], serum total antioxidant [TAG] and serum nitric oxide [NO] levels were measured. Also Liver function tests [serum alkaline phosphatase, glutamic oxalacetic transaminase and glutamaic pyruvic transaminase] were measured. In addition, kidney function tests [serum urea, creatinine and uric acid] were done. Results showed an increase in the mean of blood lead level, increase serum TBARS levels, decrease serum TAG and NG levels and increase levels of liver and kidney function tests in lead treated group. Treatment with DMSA alone resulted in reduction of blood lead levels, improvement of serum NG level but not decrease serum TBARS level and moderate decrease in the elevated liver and kidney function test parameters. Rats treated with ALA alone showed no reduction in the elevated blood lead levels, but decreased serum TBARS and improved serum NO, TAG levels, liver and kidney function tests. Rats treated with DMSA and ALA concurrently showed decrease in blood lead levels, decrease serum TBARS, increase serum NO and TAG levels to near normal level and corrected liver and kidney function tests. In conclusion administration of ALA has beneficial effect as thiol-mediated antioxidant function when given to occupationally exposed workers to lead and during treatment of lead poisoning with DMSA as it increases its efficacy

role of cinnamon and curcumin in enhancing antioxidants activity in aspirin induced hepatotoxic rats

This study was undertaken to investigate the putative antioxidant activity of cinnamon and curcumin on aspirin induced hepatotoxicity in male albino rats Aspirin [in a form of acetylsalicylic acid] was administrated to rats through the diet 4mg% for 30 days [G2] on the other hand, cinnamon and/or curcumin were administered to rats in concentration of 5% as seen in groups [G3, G4, G5]. Obtained results of G2 announced a significantly elevated [p<0.01] serum levels of aspartate transaminase [AST],alanine transaminase [ALT], alkaline phosphatase [ALP], and bilirubin as compared to the control group. On the other hand, aspirin administration resulted in significant reduction [p<0.01] in the level of total protein compared to the control group. In the liver, significantly elevated levels [p<0.01] of malondialdehyde [MDA] was observed. The analysis of antioxidant defense system [superoxide dismutase [SOD] and phospholipids hydroperoxide glutathione peroxidase [GPx-4]] revealed lower activities of these antioxidant enzymes in the liver of aspirin administered rats. All these results reported the incidence of hepatotoxicity. When rats with aspirin induced hepatotoxicity were treated with cinnamon and/or curcumin, [G3,G4,G5], serum ALT, AST, ALP, total serum protein and bilirubin levels reverted to near normal while hepatic concentration of SOD and GPx-4 were significantly increased [p<0.01], and that of MDA significantly lowered [p<0.01], when compared to aspirin administered untreated rats. These results suggest that, cinnamon and curcumin were able to significantly alleviate the hepatotoxicity induced by aspirin in rats

[ hepatotoxicity of aqueous methanol extract and fractionated-methanol extract of Phytolacca americana in male rat using perfusion method]

Phytolacca americana is a native plant in several states of USA and mostly its boiled leaves are used as a popular salad [called grandmother salad] in American diet. It grows widely in the coastal areas and forests in northern parts of Iran but is rarely used. In spite of having several medicinal properties, its side effect is digestive toxicity [especially hepatotoxicity]. To date, the hepathotoxicity of this plant from northern of Iran has not been studied. Therefore, this study was aimed to investigate the hepatotoxicity of P. americana using Isolated Rat Liver Perfusion [IRLP] system. The albino rats weighted 180-220 g were desighdted into 6 groups. Subsequently, the male rat's anesthetized using ether, were used for experiments. The inferior vena cava was cannnulated with PE-10 tubing. The portal vein was immediately cannulated with a 23 g catheter. Then the liver was perfused in site by Krebs-Henseleit buffer at 37°C with a rate of 20ml/min for 3hr. After 30-45 min of perfusion, various doses [10, 20, 40, 50, 100 mg/kg] of aqueous and methanol extracts and CHCl3, ETOAC and MEOH fraction [10, 20, 40mg/kg] were added to the buffer and perfused for 2 hr. Samples of perfused fluid were collected every 30min and analyzed for any liver injury by measuring the serum enzymes [ALT, AST]. Sections of liver tissue were also examined for pathological changes. The results showed that the activity of aminotransferase enzymes increased significantly and dose-dependently [p<0.01]. Also, methanol extract fractionates were increased compared with the control group [p<0.05]. The histopathological changes in the liver tissue were dose-dependent and confirmed the previous data. The enzymatic differences between the test groups and the control group showed the most difference at 60 min. The finding showed that the hepatotoxic effect of P. americana is dose dependent. Therefore, decreasing the administrated dose may be effective in prevention of its hepatic side effects

prophylactic effect of Nigella sativa L. On CCI[4]-treated rats

This study was designed to evaluate the prophylactic effect of Nigella sativa L. on lipid peroxidaton, antioxidant systems and liver function in carbon tetrachloridetreated rats. The rats were divided into five experimental groups: Control non-treated group, CCl[-4] intoxicated group, Nigella sativa oil+ CCl[4] group, Nigella sativa seeds + CCl[4] group and Antox + CCl[4] group. Antox was used as a reference antioxidant. All groups received CCl[4] [4 ml/Kg b.wt. in sunflower oil [1:1] Sc] as a first initial dose, then every 15 days [half dose of CCl[4]]. Nigella sativa oil [2ml/Kg b.wt./day by gavage], Nigella sativa crushed seeds [2g/100g diet] and Antox [45.22mg/Kg b.wt./day by gavage] were administered 14 days before Cd4 treatment and continued till the end of the experimental period [45 days].The CCl[4] treatment significantly increased lipid peroxide products [as measured by the concentration of plasma malondialdehyde, MDA,] erythrocyte Giutathione peroxidase [GSHPx] and liver transaminases [ALT and AST] coupled with significant decrease in whole blood Glutathione level [GSH], erythrocyte Superoxide dismutase [Cu-Zn SOD] activity, total protein and albumin levels. The positive protective effect of the test plant or Antox against the deleterious effects of CCl[4] was indicated by a well marked inhibition in malondialdehyde production, regulation of the antioxidant system, decrease in liver transaminases and increase in total protein and albumin levels. The obtained data revealed that Nigella sativa crushed seeds displayed a potent antioxidant effect that super exceeds those recorded by either Antox or Nigella sativa oil

Comparative hepatotoxic study between acyclovir and famciclovir in adult male albino rats

Eighty adult male albino rats, which were divided into four groups, ninety rats each. Group 1 [negative control group], Group 2 [positive control group] gavaged orally with distilled water, Group 3 [Acyclovir group] gavaged orally with Acyclovir 432 mg/kg B. wt. once daily for 4 weeks and lastly Group 5 [Famcyclovir] gavaged orally with Famcyclovir 135 mg/kg B. wt. After 4 weeks, blood samples, for estimation of serum albumin and alkaline phosphatase, were withdrawn from each rat and then rats were sacrificed. Liver specimens were obtained for histopathological examination by light microscope after staining with haematoxylin and eosin and special stain for immunohistochemical detection of Appoptotic changes. As compared to control groups and Famcyclovir group, Acyclovir group showed significant decrease of serum albumin, elevation of alkaline phosphatase activity associated with a severe apoptotic changes as evidenced by Bc12 overexpression in liver cells. The present study doesn't recommend the use of Acyclovir in patient with liver impairment and if strongly indicated, it's wiser to use Farmcyclovir

[Alanin aminotransferase activity in veterans exposed to sulfur mustard]

Until now, few studies have focused on late effect of sulfur mustard on the liver; at present there is no data published on liver enzymes in sulfur mustard exposed veterans. The current study was conducted with the aim of determining alanine aminotransferase [ALT] levels in veterans exposed to sulfur mustard. In this cross-sectional study, 263 sulfur mustard exposed veterans were selected from among individuals referring to the respiratory clinic in Bagiyatallah hospital in 2005. ALT was determined in all subjects. Demographic data, exposure related variables, respiratory status and Body Mass Index [BMI] were collected. ALT over 40 unit/liter was considered as abnormal. From a total of 263 sulfur mustard exposed veterans, 43 [16.3%] patients had an elevated ALT level. Range of ALT was 3-94 with a mean [SD] of 26.43 +/- 15.22 unit/liter. ALT was correlated with the BMI [r=0.153, p=0.013]. ALT was not significantly correlated with age, grading of chemical and overall disability. Mean ALT levels in patients with BMI > 25 [28.81 +/- 15.05] were significantly higher than those with BMI less than 25 [21.93 +/- 14.58] [p=0.001]. Mean ALT level was higher in those with FEV1/FVC, in comparison to others [p<0.05]. ALT was not significantly correlated with other study variables [p>0.05]. Although any conclusion of the impact of mustard gas on ALT needs a controlled study, we mean while suggest serial measurement of the activity of this enzyme and other measures of liver status

Assessment of histopathological and histochemical changes in liver of pregnant female rats and their fetuses following ciprofloxacin administration

The present study was carried out on female albino rats weighing 130-160 g, through two periods of gestation [day 1 or day 6 up to day 19 of pregnancy] representing four experimental groups and one control group. Experimental animals were given daily oral dose [57 mg/Kg b.w., therapeutic dose] or 114 mg/K b.w. [double therapeutic dose] of ciprofloxacin [CPFX]. Dissection was performed on day 20 of pregnancy. Histological changes in liver sections of pregnant rats were in the form of dilatation of central and portal vein, and sinusoidal spaces; appearance of macrophages and Kupffer cells in sinusoidal spaces and congestion in blood vessels, The hepatocytes showed cytoplasmic vacuolation and nuclear unrest, Inflammatory leucocytic infiltration and focal fibrosis were also observed. Liver sections of fetuses obtained from pregnant rats treated with the [CPFX] revealed histopathological alterations similar to their mothers. Total proteins content decreased by -5.59% in GI, -8.60% in GIII and -6.83% in GIV. Group two [GII] recorded a lower level in total protein [-0.62%]. Moreover a significant decrease in total protein of fetuses was manifested being 17.96%, 13.28%, 22.62% and 21.87% for the four groups, respectively. The hepatocytes of mothers exhibited a significant decrease in DNA content presenting 9.42%, 3.46%, 10.40% and 7.51,% in the four groups respectively. In the hepatocytes of their fetuses the DNA content recorded a significant decrease of 10.43%, 9.34%, 18.68% and 17.58% for the four groups respectively. These results emphasize the toxicity of CPFX and its teratogenic effects

Modulatory effect of the red sea soft coral extracts on hepatotoxicity induced by carcinogenic agents in rat model

Recently, there has been a growing interest in the presence of pharmacologically active components in the aquatic environment. Soft corals are prominent reef organisms in the Red Sea and are prolific sources of terpenoids, especially cembranoid diterpenes. The objective of this study was to investigate the inhibitory effect of the extract from the aqueous MeOH [80%] extract of each of the three Red Sea soft corals: Sinularia polydactyla, Sarcophyton trocheliophorum and Xenia macrospiculata on hepatic toxicity induced by the carcinogenic agents 7, 12 dimethyl benz [a] anthracene [DMBA] and 12-Otetradecanoyl phorbol-13- acetate [TPA] in adult female rats. The results revealed that the liver functions were markedly improved and the levels of tumor markers as well as the inorganic free radical "NO" in serum were significantly decreased as a results of the treatment with three coral extracts. Moreover, treatment of DMBA and TPA-intoxicated groups with the coral extracts resulted in significant reduction in hepatic oxidative stress in concomitant with significant elevation in hepatic SOD activity as compared to the group intoxicated with DMBA and TPA only. Serum estradiol and corticosterone levels were high significantly decreased in the groups intoxicated with DMBA and TPA and treated with the three extracts compared to the group intoxicated with DMBA and TPA only. The soft coral Xenia macrospiculata extract, exerted the highest potential to inhibit hepatotoxicity induced by the tested carcinogenic agents. Each of the soft coral extracts has played a vital role in modulating the severe hepatotoxicity caused by the administration of the two carcinogenic agents DMBA and TPA. The liver functions were significantly promoted beyond normal status, while the hepatooxidative stress was markedly depressed. These results may provide new concept for development of effective therapies for some diseases involving hepatotoxicity

[ survey of Teucrium Folium toxicity effect on liver and serum lipoproteins in normoglycemic male rats]

Liver is an important organ in carbohydrates and fatty acids oxidation and to clear toxic agent. Teucrium Polium is an herbal medicament used in traditional medicine without considering its side effects. The aim of this survey was to study the toxic effects of Teucrium Polium on serum levels of liver enzymes, lipoproteins and blood sugar. The survey was carried out on 20 normoglycemic male rats with body weight, ranging from 200-280 gr that were divided randomly in two equal groups randomly. Test group were given Teucrium Polium extract [D=1/09] through gavages for 4 weeks. Control group received the same volume of tap water. At the end of the course, liver enzymes, serum lipoproteins and blood sugar were measured. Data obtained were analyzed by SPPS software v.12 and mean values were compared with student t-test. The results were expressed as mean +/- SD and statistical difference considered meaningful if P<0.05. The results of this survey showed that AST, ALT, and ALP, values of test group were significantly higher than that of the control group but other factors, which were evaluated in test and control group, did not show significant difference. This survey revealed Teucrium Polium use in male rats led to liver Toxicity by increasing liver enzyme value

in vivo protective effects of silymarin on DMN-induced hepatotoxicity in rats

Dimethyl nitrosamine [DMN] is a very potent chemical carcinogen which occurs naturally in the environment and in a wide variety of food stuffs, and can be formed in the body by nitrosation of secondary or tertiary amines in the presence of nitrite, nitrate or nitrogen oxides. Silymarin is a powerful antioxidant and has a potent free radical scavenging activity, said to protect cells of liver, brain and other cells in the body from toxins. To examine the in vivo protective effects of silymarin on the induced oxidative damage in livers of DMN-intoxicated rats histologically and immunohistochemically. The ability of silymarin to protect and detoxify DMN toxicity was examined in rat livers. Dietary pretreatment of rats [body weight 125-135 g] with silymarin [0.9 mg/g body weight] for two weeks prior to the intraperitoneal injection of DMN, reversed the hepatotoxic effects of DMN, as examined histologically. DMN in two doses of 15 micro g/kg or 25 micro g/kg was injected. After DMN treatment, the animals were fed with diet with silymarin or without for 48 hours. Rats were sacrificed 48 hours after DMN injection. The immunoreactivity of cells of rats' livers was examined for antibodies of heat shock protein 70 [HSP70] [HSPs are a family of proteins that are triggered to be induced when a cell undergoes environmental stresses including oxidative stress, pathogenic conditions ...etc]. The histological evaluation revealed prominent changes in groups received DMN in high dose more than low dose. Treatment with silymarin reversed this effect. The immunohistochemical assay for the stress-protective proteins "HSP70" showed that treatment with silymarin triggered more expression of this protein. Silymarin can provide substantial protective effect against DMN-induced hepatic oxidative damage with therapeutic potential to be used in human

Pharmacokinetics effects of some insecticides on white albino rats

The treatment of adults' female albino rats with Maximum Residue Limit [MRL] to tomato fruits of the three organophosphorus insecticides namely, primiphos-methyl, chloriphos-methyl and fenitrothion [1, 0.5 and 0.5 ppm] respectively on different periods [from 1. 6, 12, 24, 48, 96 hours and 7 days] to indicate and follow-up the effect of these insecticides on liver and kidney functions. A significant increasing activities of Aspartate Amino Transferase [AST] were found. No changes in Alanine Amino Transferase [ALT] and Alkaline phosphatase activities were observed in treated rats by the MRLs of the tested insecticides as compared with control. The data gathered showed that there were no significant changes in creatinine levels and urea concentrations of the treated rats at the different periods after dosing by the MRL of the tested insecticides. The data also clearly indicated an insignificant decrease in total protein levels, observed in rats treated by MRL of the tested insecticides after 1, 6, 12, 24, 48, 96 hrs and 7 days of treatment. Cholesterol level displayed slight or insignificant increasing in rats which were treated with the aforementioned insecticides. Generally treating rats by MRL of the prementioned insecticides resulted in a small [deleterious] effect on some biochemical parameters after 7 days of treatment. No effects have been detected at the first hours of the experiments

alpha-lipoic acid protects against acetaminophen-induced hepatotoxicity: inhibition of FAS mediated liver apoptosis

Acetaminophen [APAP] overdose causes acute liver injury in humans and animals. This study was carried out to investigate whether the lipid soluble antioxidant -lipoic acid [ALA] can protect against APAP-induced hepatotoxicity. Rats were treated with APAP [1q/kg] I.P. either alone or with ALA [100mg/ kg] at the same time for 24hr. Acetaminophen caused a time-dependent increase in the plasma levels of ALT enzyme activity; hepatocytes LDH leakage; nitric oxide [measured as NO2 -/NO3-] levels and caused severe hepatic necrosis. It also decreased liver contents of reduced glutathione [GSH]. In addition, APAP caused hepatic DNA fragmentation as assessed by agarose gel electrophoresis technique; increased apoptotic index [assessed by TUNEL assay] and liver Fas expression [assessed immunohistochemically]. Co-administration of ALA with APAP resulted in protection against APAP-induced hepatic injury as presented by the significant decrease in the hepatocellular enzyme release [ALT and LDH] and attenuation of hepatocytes apoptosis and necrosis. The hepatoprotective effect of ALA against APAP-induced liver damage was found to be due to several mechanisms including attenuation of hepatic lipid peroxidation [measured as MDA], increase hepatic contents of GSH, and/or decrease liver Fas expression, decreased apoptotic cell death and DNA damage. These results may recommend the use of ALA in treatment of APAP-induced hepatotoxicity as a new line therapy

Texicological, histopathological and ultrastructural study of the protective effects of some antioxidants on sodium valproate induced hepatotoxicity in rats

Valproic acid [VPA] is well known for its broad spectrum antiepileptic activity and is gaining popularity as a component in antipsychotic therapy. VPA may have limited use due to the possible risk of hepatotoxicity. The aim of the present work was to investigate the hepatotoxic effect of VPA and to evaluate the protective role of deferoxamine and L-carnitine. The levels of malonaldehyde [MDA], antioxidant enzymes [catalase and glutathione -S-transferase] and liver triglycerides were measured in the liver tissues. In addition, serum levels of liver enzymes and plasma triglycerides were measured. Histological and ultrastructural changes in the hepatocytes were studied. The results showed that, VPA- induced hepatotoxicity was in the form of micro vesicular steafosis. Biochemically, evidence of oxidative stress namely, elevated levels of MDA, catalase and glutathione -S- transferase were found. Increased levels of liver enzymes and plasma and liver triglycerides were also detected. Co-administration of deferoxamine with VPA resulted in protection of the hepatocytes against VPA induced hepatotoxicity. Co-administration of L-carnitine with VPA was associated with better results than deferoxamine histologically, ultrastructurally and biochemically. In conclusion, the use of L-carnitine as an antioxidant in protecting against valproat induced hepatotoxicity should be encouraged