Friday E. Uboh

Endosulfan-induced hepatotoxicity is route of exposure independent in rats

Endosulfan is an important hepatotoxic agent that generates free oxygen radicals in liver. With the widespread use of endosulfan in agriculture, human beings are most likely to be exposed to it by eating food contaminated with endosulfan, exposure to its low levels by skin contact with contaminated soil, smoking cigarettes made from tobacco that has endosulfan residues on it, or by nose and whole body inhalation exposure in the farms during its application. Since endosulfan is a frequently used pesticide, and the incidence of toxic injury to the liver tissue in relation to its widespread use reported in the literature, we considered it necessary to investigate whether endosulfan-induced liver injury could be route of exposure dependent. Eighteen mature male albino Wistar rats, weighing between 180 and 220 g, were used in this study. The hepatotoxic effects of oral administration of endosulfan (5 mg/kg body weight) daily for 30 days, and 30 days whole body inhalation exposure to ungraded concentration of endosulfan were investigated in rats using serum liver enzymes and histopathological assay. At the end of the experimental period, serum alanine aminotransferase, aspartate amino transferase, alkaline phosphatase, and creatine kinase activities obtained for the group of rats exposed orally to endosulfan were not significantly different (p 0.05) from the activities obtained for rats exposed by whole body inhalation. However, the activity of these enzymes obtained for the rats exposed to endosulfan by both oral and inhalation routes were significantly increased (p 0.05) compared, respectively, to the control. Also, on microscopic examination, the liver tissues of experimental groups exhibited severe damage histopathologically. The results of the enzyme and histological analyses showed that both oral and whole body inhalation exposure to endosulfan may cause liver tissue damage in rats. The exposure to endosulfan in rats caused liver tissue damage independent of the route of exposure.Endosulfan is an important hepatotoxic agent that generates free oxygen radicals in liver. With the widespread use of endosulfan in agriculture, human beings are most likely to be exposed to it by eating food contaminated with endosulfan, exposure to its low levels by skin contact with contaminated soil, smoking cigarettes made from tobacco that has endosulfan residues on it, or by nose and whole body inhalation exposure in the farms during its application. Since endosulfan is a frequently used pesticide, and the incidence of toxic injury to the liver tissue in relation to its widespread use reported in the literature, we considered it necessary to investigate whether endosulfan-induced liver injury could be route of exposure dependent. Eighteen mature male albino Wistar rats, weighing between 180 and 220 g, were used in this study. The hepatotoxic effects of oral administration of endosulfan (5 mg/kg body weight) daily for 30 days, and 30 days whole body inhalation exposure to ungraded concentration of endosulfan were investigated in rats using serum liver enzymes and histopathological assay. At the end of the experimental period, serum alanine aminotransferase, aspartate amino transferase, alkaline phosphatase, and creatine kinase activities obtained for the group of rats exposed orally to endosulfan were not significantly different (p ≥ 0.05) from the activities obtained for rats exposed by whole body inhalation. However, the activity of these enzymes obtained for the rats exposed to endosulfan by both oral and inhalation routes were significantly increased (p ≤ 0.05) compared, respectively, to the control. Also, on microscopic examination, the liver tissues of experimental groups exhibited severe damage histopathologically. The results of the enzyme and histological analyses showed that both oral and whole body inhalation exposure to endosulfan may cause liver tissue damage in rats. The exposure to endosulfan in rats caused liver tissue damage independent of the route of exposure.

Vitamins A and E reverse gasoline vapors-induced hematotoxicity and weight loss in female rats

In this study, gasoline vapors-induced hematotoxicity, growth-depression and weight-loss reversal effect of vitamins A (retinol) and E (α-tocopherol) was assessed in female Wistar albino rats. The rats were exposed to gasoline vapors (17.8 2.6 cm 3/h/m3/day), 6 hours/day, 6 days/week, for 20 weeks. Vitamins A and E at prophylactic dosage (400 and 200 IU/kg/day, respectively) were orally administered to the rats, separately, in the last 2 weeks of exposure. The levels of hemoglobin (Hb), hematocrit or packed cell volume (PCV), red blood cells (RBC), growth rate and weight gain in the rats exposed to the vapors were significantly lower (p < 0.05) compared, respectively, to the levels obtained for control rats. On the other hand, the levels of white blood cells (WBCs) in the test rats were significantly higher (p < 0.05) compared, respectively, with the level obtained for female control rats. These observations indicated that exposure to gasoline vapors may cause hematotoxicity, growth depression and weight loss in female rats. However, administration of vitamins A and E was observed to produce a significant recovery (p < 0.05) in hematotoxicity, growth depression and weight loss observed to be associated with exposure to gasoline vapors, although the rats administered with vitamin E were noted to respond more favorably than those administered with vitamin A. This suggests that although retinol and α-tocopherol may be used to reverse or prevent hematotoxicity, growth depression and weight loss in subjects exposed to gasoline vapors, the reversal potency of α-tocopherol is higher than that of retinol.

Comparative Hepatoprotective Effect of Vitamins A and E Against Gasoline Vapor Toxicity in Male and Female Rats

Background Plasma alanine transferase(ALT), aspartate transferase(AST), α-glutamyl transferase(GGT), and alkaline phosphatase(ALP) activities are known biomarkers in assessing hepatic functional integrity. A remarkable rise in the activities of these enzymes normally signifies hepatotoxicity of chemical agent(s) in the biological system. Exposure to 17.8 cm3h-1m-3 of PMS blend unleaded gasoline vapors (UGV) for 6 hr/day, 5 days/week for 20 weeks have been reported to cause hepatotoxicity in rats. Methods In this study, the comparative hepatoprotective effect of vitamins A (retinol) and E (α-tocopherol) against UGV-induced toxicity was assessed in male and female rats. Retinol and α-tocopherol at prophylactic dosage (400 and 200 IU/kg/day, respectively) were separately administered orally to the test rats concomitant with exposure to UGV in the last two weeks of the experiment. Results The results of this study indicated that exposure to UGV caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in male and female rats. Oral administration of prophylactic doses of retinol and α-tocopherol produced a significant decrease (P < 0.05) in the activities of these parameters in male and female test rats, compared with the non-treated test rats; but insignificant increase(P ≥ 0.05), compared with the control. However, the hepatoprotective effect of α-tocopherol was observed to be more potent than that of retinol. Conclusions The result of this study demonstrated that the hepatoprotective potency of α-tocopherol against gasoline vapors toxicity was higher than that of retinol in male and female rats, although the female gender of the animal model responded to treatment with both vitamins better than the males. Hence, the work suggested the beneficial effects of both vitamins against hepatotoxicity in individuals frequently exposed to gasoline vapors.

Comparative Effect of Withdrawal from Exposure on Gasoline and Diesel Induced Nephrotoxicity in Male Albino Wistar Rats

Exposure to gasoline and diesel has been reported to induce nephrotoxicity in rats. This study was designed to assess the effect of withdrawal from exposure on the nephrotoxic effects associated with oral exposure to gasoline and diesel in male rats. Four groups of the experimental test rats were respectively exposed orally to diesel and gasoline solvents (4.0 mg/kg/day, 6 days/week) for 60 days, after which two respective groups were sacrificed for nephrotoxicity assay while the remaining two groups were withdrawn from exposure for the next 60 days before sacrificing them for biochemical assay. The results showed that oral exposure to diesel and gasoline induced a significant (p<0.05) increase in serum creatinine, urea, blood urea nitrogen (BUN) and kidney tissue malondialdehyde (MDA), as well as decrease in kidney tissue reduced glutathione (GSH) concentrations in rats. However, the percentage increase in serum creatinine, urea, BUN, kidney tissue MDA, and decrease in kidney tissue GSH concentrations recorded for rats exposed to diesel (300.1 ± 30.8, 130.3 ± 18.5, 125.6 ± 16.4, 141.8 ± 10.4 and 75.0 ± 8.6 percents, respectively) were significantly higher (p<0.05) compared to the percentages recorded for rats exposed to gasoline (150.0 ± 17.5, 80.3 ± 13.2, 72.1 ± 11.4, 120.9 ± 15.2 and 61.5 ± 10.1 percents, respectively). The result of this study also showed that withdrawal from exposure reverses the levels of serum creatinine, urea, BUN, and kidney tissue MDA and GSH to the levels approximately within the control range. This study confirms that oral exposure to diesel and gasoline may be a risk factor for nephrotoxicity, with diesel being more nephrotoxic than gasoline, and that withdrawal from exposure for equal duration of the exposure period is capable of reversing the induced nephrotoxicity in rats.

Effect of folic acid and vitamin B(12) administration on phenytoin induced toxicity in rats.

Folic acid and vitamin B12 are very important vitamins needed for normal cellular metabolic activities. The effects of folic acid and vitamin B12 on liver integrity of growing Wistar albino rats following therapeutic dose of phenytoin administration were investigated. The activities of serum AST, ALT, ALP were investigated. Serum total protein level and lipid profile were also measured as indices of biochemical changes. The ingestion of phenytoin alone in rats significantly reduced serum protein while AST, ALT activities incresed as compared to the control (P<0.05). Supplementation of phenytoin with oral administration of 70microgram/kg body wt of folic acid resulted in a significant reversal in serum total protein and suppression in serum AST and ALT activities. Vitamin B12 supplementation did not afford any significant protection against the effect of phenytoin ingestion but rather phenytoin toxicity was exacerbated in this study. However, the combined effects of vitamin B12 and folic acid ameliorated the effects of phenytoin on serum enzymes of experimental rats. The effect of combination of phenytoin with folic acid or folic acid and vitamin B12 is an interesting finding. Supplementation of phenytoin with folic acid or combination of these vitamins may be recommended for the purpose of ameliorating the adverse biochemical changes which are associated with phenytoin therapy. Further work is ongoing to help elucidate the effects of phenytoin and these vitamins on oxidative stress inducing mechanism.

Withdrawal from Exposure Reverses Hematotoxicity and Hepatotoxicity Caused by Oral Exposure to Nitrocellulose Thinner in Male Rats

Nitrocellulose thinner (nct) is one of the commonly used industrial chemical solvents. Individuals involved in furniture, paint, automobile manufacture and repairs occupations, and those living around these workplace environments are at the risk of exposure to nct’s constituents ubiquitously released into the environment. Oral exposure to this solvent has been reported to cause haematotoxicity and hepatotoxicity in rat model. This study assessed the impact of withdrawal from exposure, on nct induced-haematotoxicity and hepatotoxicity in male albino Wistar rats. Four groups, of twelve male rats each, were orally exposed to graded concentrations of nct for 28 days. After the 28th day of exposure, six rats in each group were sacrificed and blood samples collected for nct inducedhaematotoxicity and hepatotoxicity analyses. The remaining six rats in each group were withdrawn from exposure for the next 28 days, after which they were sacrificed, blood samples collected and analyzed for any possible recovery effect from exposure-induced haematotoxicity and hepatotoxicity. The results confirmed that exposure of male rats to nct for 28 days caused a significant (P<0.05) concentration-dependent increase in haematotoxic and hepatotoxic indices, compared to the control. However, 28 days withdrawal from exposure produced a significant (P<0.05) reduction in the recorded haematotoxic and hepatotoxic indices, compared to the nct exposed groups. The results obtained for rats withdrawn from exposure were within the same range as those obtained for the control group, indicating that withdrawal from exposure may reverse the haematotoxic and hepatotoxic effects associated with exposure to nct in male rats.

Protective Effect of Vitamins C and E against Nitrocellulose Thinner InducedNephrotoxicity in Albino Wistar Rats

Effect of vitamins C (vitamin C) and E (vitamin E) on nitrocellulose thinner (NCT)-induced nephrotoxicity in male rats was assessed. Six groups of six rats each, were orally administered 0.5 ml distilled water, 0.5 ml soybean oil, 40.0 mg NCT/kg bwt, 40.0 mg NCT/kg bwt+200 mg vitamin C/kg bwt, 40.0 mg NCT/kg bwt+200 IU vitamin E/kg bwt, and 40.0 mg NCT/kg bwt+200 IU vitamin E+200 mg vitamin C/kg bwt, respectively, for 30 days. The animals were sacrificed, 24 hours after last experimental treatments, blood and kidney tissues were collected for analyses of indicators of nephrotoxicity using standard methods. The results showed a significant (p 0.05) difference was recorded for these parameters in rats receiving soybean oil, compared with control rats receiving distilled water. These results indicated that exposure to NCT induced nephrotoxicity in rats. It was also observed that administration of vitamin C and vitamin E, in combination and singly, to rats exposed to NCT produced relatively normal renal histological status, and levels of the assayed serum nephrotoxicity indicators within the control range; suggesting vitamin C and vitamin E to be potent in preventing NCT-induced nephrotoxicity in rats. However, comparative percentage decreases (CPD) in sCr, uric acid, K+ and HCO3 - indicated that combined vitamin C and vitamin E administration produced a higher protective potency than single administration; and that vitamin C produced a higher potency than vitamin E against NCT-induced nephrotoxicity.

Analysis of bioactive constituents of n-hexane and methanol fractions of Vernonia calvoana Extracts using Gas Chromatography- Mass Spectrometry

Aim: Bioactive constituents of n-hexane and methanol fractions of Vernonia calvoana (VC) leaves were evaluated using Gas chromatography-Mass spectrometry. Method: The leaves were harvested, cleaned and air dried for 7 days. They were ground to yield 5 kg weight powder which was macerated and extracted in 8000 mL of 80% ethanol for 48 hours, yielding 310.3g (6.2%) of crude extract after evaporation of the solvent. The paste (251.8g) was subjected to column chromatography over silica gel (mesh 60 – 120 μm) and eluted with 1.5L of n-hexane and methanol respectively. The fractions were analyzed for bioactive constituents using Gas chromatography-Mass spectrometry (GC-MS) (30 m x 0.25 mm ID x 0.25 μm film thickness). Result: The results of GC-MS analysis showed the presences of twelve compounds with phytol (46.67%), 8,11,14-eicosatrienoic acid (33.40%), octadecanoic acid (11.25%), pentadecane carboxylic acid (10.69%), 9, 12, 15-octadecatrien-1-ol (8.12%) and ethyl palmitate (7.68%) in the n-hexane fraction, while methanol fraction was observed to have 14 compounds with oleic acid (33.40%), hexadecanoic acid (12.49%), 2-butanone (14.32%), palmitadehyde (8.36%), 11-octadecenoic acid (5.56%), Z-4-nonadecen-1-ol-acetate (5.36%) and limonene Oxide (4.37%) as well as other compounds in trace concentrations. Conclusion: it may be concluded from the results that, extracts of Vernonia calvoana contain various bioactive components that may be exploited as a good source of new drug for pharmaceutical industries.