Mega Dose of Vitamin C Augments the Nephrotoxicity of Paracetamol (original) (raw)

Effects of vitamin C on liver and kidney enzymes and some biochemical parameters against paracetamol induced hepato-nephrotoxicity in rats

Sirte University Scientific Journal(Applied Sciences) , 2021

The current investigation aims to study the effects of VC against hepato-nephrotoxicity induced by PCM in rats. Forty male rats were divided into five groups with eight rats in each group. Group I (normal control): received distilled water orally, group II; received 500 mg/kg of VC, group III; received 500 mg/kg of PCM, group IV (protective group); received VC for 7 days, and then PCM for another 7 days, and group V treated with a combination of VC and PCM for 14 days. Results showed that a significant decline in percentage of change in body weights of treated rats with the PCM as compared to control rats while, animals that given VC with or before taken PCM showed a significant increase when compared with the PCM group. PCM caused significantly increased the liver and kidney enzymes (AST, ALP, ALT, TB, creatinine, urea, and uric acid) as well as cholesterol, and glucose levels when compared with normal rats. Whereas, animals in the protective group showed decreased liver and kidney enzymes and cholesterol, and glucose levels as compared to the PCM group. In conclusion, the results of this study demonstrate that VC was effective in reducing the hepato-nephrotoxicity caused by PCM in rats.

The effect of paracetamol on the kidney tissues of male albino rats and the protective effect of vitamin C

مجلة البيان العلمية, 2021

Vitamin C (VC) is a natural antioxidant found in citrus, soft fruits and leafy green vegetables and has shown protective effects against nephrotoxicity damage caused by different drugs. This study aimed to the possible protective effects of VC against renal damage induced by PCM in rats. Forty male rats were divided into five groups: Group (1) as control; receiving distilled water orally, group (2); receiving 500 mg/kg of VC. Group (3); receiving 500 mg/kg of PCM. Group (4) (protective group); receiving VC for 7 days, and then PCM for another 7 days, and group (5) treated with a combination of VC and PCM for 14 days. Renal tissue of PCM rats showed degeneration of renal corpuscles with the widening of Bowman's space, peritubular capillary dilatation and congestion, desquamation renal tubular epithelium with damage to the brush borders of the cell and presence of debris in the tubular lumen, and pyknotic nuclei of tubular cells. However, protective rats showed the nearly normal renal structure of both cortex and medulla, but VC + PCM rats showed some modifications in kidney structures ranging. In conclusion, VC as an antioxidant can protect kidney from PCM induced tissue damage.

The antioxidant effects of vitamin C on liver enzymes: aspartate aminotransferase, alanine aminotranferease, alkaline phosphatase and gamma-glutamyltransferase activities in rats under Paraquat insult

Journal of Xenobiotics, 2013

Paraquat (PQ) is a bipyridylium herbicide; applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the liver enzymes [aspartate aminotransferase (SGOT), alanine aminotranferease (SGPT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT)] of rats under this toxic insult. Male rats in groups (A, B, C and D) were intraperitoneally injected with different sublethal increasing doses (0, 0.02, 0.04 and 0.06 g/kg body weigh) of PQ respectively on monthly basis. Subsequently, the subgroups (A 2 , B 2 , C 2 and D 2) were given orally, 200 mg/L vitamin C, while the subgroups A 1 , B 1 , C 1 , and D 1 , received only water. Four animals per subgroup were decapitated on monthly basis and blood samples taken for enzyme assay. The parameters studied were-SGOT, SGPT, ALP and GGT-liver enzymes. The dose and time dependent PQ toxicity effect resulted in highly elevated Liver enzymes activities. The subgroups on vitamin C had significantly lower enzyme activities when compared to the same subgroups on only PQ insult. But the values were high when compared to the control subgroups (A 1 and A 2). These results were indication that vitamin C when given at moderate doses and maintained for a longer period could be a life saving adjunct to toxic insult.

Vitamin C in-vivo Effect on Liver Enzymes and Some Endogenous Antioxidants in Paracetamol-Induced Model of Liver Toxicity on Wistar Rats

Journal of Applied Sciences and Environmental Management, 2019

This study aimed at assessing the in-vivo effect of Vitamin C on liver enzymes and some endogenous antioxidants in paracetamol-induced model of liver toxicity on Wistar rats. The rats were grouped into four groups of five animals each; groups 1 and 2 were control (positive and negative), while group 3 and 4 received vitamin C 500 mg/kg and silymarin 100 mg/kg respectively. Dosing was oral and daily for 6 days according to their body weights. All the animals except the positive control group (Group 1) were administered paracetamol 3 g/kg on the 7 th day, and then observed for 24 hours before sample collection for biochemical indices and liver histological studies. Paracetamol caused a significant (p<0.05) increase in liver enzymes, significant (p<0.05) decrease in antioxidant enzymes, and necrosis in liver tissues when compared to the control. Administration of 500 mg/kg Vitamin C prior to induction of liver damage by PCM resulted in significant (p<0.05) decreased liver enzyme and well as an increase in the antioxidant enzymes. Pre-treatment of the animals with vitamin C showed a reversal of the toxic effect of paracetamol on the rats.

The preventive effect of vitamin C on the cellular and functional integrity of kidney cells in rats following repeated exposure to paraquat

Journal of Xenobiotics, 2014

Paraquat (PQ) is a bipyridylium herbicide that is applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the cellular integrity of kidney function in rats following repeated exposure to PQ. Ninety-six male rats, grouped twelve rats per subgroup (A, A vit.c , B, B vit.c , C, C vit.c , D and D vit.c) were intraperitoneally injected with different sublethal increasing doses (0, 0, 2, 2, 4, 4, 6 and 6 mg/kg body weight) of PQ respectively on biweekly (14 days) intervals over a period of three months (84 days). Subsequently, the subgrouped animals (A vit.c , B vit.c , C vit.c and D vit.c) were maintained orally with 1 g/L vitamin C, while the other subgrouped animals (A, B, C and D) received drinking water with negligible vitamin content throughout the study period. At the end of each monthly (28 days) treatment, four animals per subgroup were selected. Urine samples were collected from each of the selected rats, after which each of the animals were anaesthetized with gaseous isoflurane and 5 mL of blood samples were collected using cardiac puncture procedure. The animals were later decapitated and their kidneys harvested. The samples collected were analyzed for urine [specific gravity (SG), pH, protein and glucose], blood (urea, creatinine, total protein and glucose), and the histological studies on kidney slides. The dose and exposure-time dependent PQ toxicity resulted in the reduction in urinary pH, elevation in urinary SG, and the detectable presence of protein and glucose in urine. It also caused normalization of serum total protein and glucose values with restoration of the renal function of treated rats. These findings clearly show that vitamin C has an important role to play in the body's antioxidant defense system. Its use caused normalization of the biochemical and histological parameters studied and restored the health status of the affected animals.

Antioxidative stress effects of vitamins C, E, and B12, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats

Drug Design, Development and Therapy

Background: Several vitamins, including C, E, and B 12 , have been recognized as antioxidants and have shown hepatoprotective effects against the hepatotoxicity caused by acetaminophen (APAP) overdose. The current investigation aims to study the effect of these vitamins and their combination in protecting the liver from APAP hepatotoxicity in rats. Materials and methods: An in vitro model of freshly isolated rat hepatocytes was utilized for assessing hepatocyte mitochondrial activity conducted by cell proliferation assay (MTT). The isolated hepatocytes were treated with vitamin C, vitamin E, vitamin B 12 and their combination, with and without further addition of toxic concentrations of APAP. In addition, an in vivo experiment was carried out on Sprague Dawley rats treated intraperitoneally for 8 days with emulsions of the vitamins or their combination prior to injecting them with APAP. Results: In vitro results showed that vitamins C and B and the combination preparation significantly increased the percentage of hepatocyte mitochondrial activity, both with and without the addition of APAP (P,0.01). The mitochondrial activity in the isolated cultured hepatocytes was further enhanced with APAP addition. In vivo, the vitamins and their combination effectively reduced APAP-induced serum liver enzymes levels, namely ALT, AST, and ALP, and also attenuated oxidative stress and lipids peroxidation confirmed by the results of glutathione, superoxide dismutase, and maloondialdehyde. Conclusion: Pretreatment with vitamins C, E, B 12 , or their combination was found to be beneficial in preventing in vivo hepatic oxidative stress induced by APAP overdose. Vitamin C on its own showed superior protection against APAP-induced liver injury in rats compared to the other vitamins. The proliferation of APAP-intoxicated liver cells in vitro was highest when protected with the vitamins' combination.

Comparative effects of vitamin C and vitamin E pre-treatment in acute paracetamol induced toxicity on the liver of rats

Paracetamol as an analgesic can also cause hepatotoxicity at high doses. This study is aimed at determining which of the two vitamins (Vitamin C or Vitamin E) is more potent in moping out the free radicals produced by paracetamol toxicity. Forty-eight male albino rats were used as my experimental model. The comparative hepatoprotective effect of vitamins C and E against paracetamol-induced toxicity was assessed in these rats. Vitamin C and Vitamin E at prophylactic dosage (80 mg / 2.4 ml, 90 mg / 2.7 ml, 100 mg / 3.0 ml and 110 mg / 3.3 ml respectively) were separately administered orally to the test rats concomitant with induced-paracetamol toxicity. Paracetamol toxicity was observed to increase significantly (P < 0.05) activities of serum ALT, AST, and ALP in male albino rats. Oral administration of prophylactic doses of ascorbic acid and α-tocopherol decreased significantly (P < 0.05) activities of these parameters in male albino rats, compared with the non-treated test rats; but insignificant increase (P ≥ 0.05), compared with the control. Vitamin C and Vitamin E are hepato protective substances although Vitamin E is likely more potent than Vitamin C in moping of free radicals produced.

Histopathological study on the protective effect of vitamin C against paracetamol-induced acute hepatic damage in rat.

Global Libyan Journal , 2021

Paracetamol (PCM) as analgesic drugs makes hepatotoxicity damage. Vitamin C (VC) has been recognized as an antioxidant and has shown protective effects against hepatotoxicity damage caused by paracetamol. The current investigation aims to study the possible protective effects of VC against hepatic damage induced by PCM in rats. Forty male rats were divided into five groups: The primary group as control; receiving distilled water orally, the second group; receiving 500 mg/kg of VC. The third group; receiving 500 mg/kg of PCM. The fourth group (protective group); receiving VC for 7 days, and then PCM for another 7 days, and the last group treated with a combination of VC and PCM for 14 days. The liver tissues after administration of PCM alone showed different changes such as disrupted lobular architecture with degenerating hepatocytes, dilated congested central vein, and mononuclear cellular infiltration. While the protective group preserved the general architecture and lacked evidence of major morphological. Additionally, VC with PCM showed some alterations in the liver architecture. In conclusion, the results of this study demonstrate that VC was effective in reducing the hepatic damage caused by PCM in male albino rats.

Effect of Vitamin C (Ascorbic Acid) as an Antioxidant in Reducing Cellular Injury Following Renal Reperfusion in Wistar Rats

Hong Kong Journal of Nephrology, 2009

Background: Renal ischemia-reperfusion (I/R) injury occurs as a result of the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS cause oxidative stress, which results in an imbalance between oxidants such as ROS and antioxidants. The objective of this study was to evaluate the protective effect of the antioxidant vitamin C compared to the effect of vitamin E on renal I/R. Methods: Wistar albino rats were divided into six groups. There were three control groups: Group 1-normal control; Group 2-sham control; Group 3-untreated experimental control. There were three experimental groups where rats were pretreated with a vitamin for 30 days: Group 4-pretreated with vitamin E; Group 5-pretreated with vitamin C; Group 6-pretreated with a combination of vitamins E and C. On day 31, all groups except normal and sham control underwent 60 minutes of renal ischemia followed by reperfusion for 10 minutes. After this, the kidney was removed and homogenized. The homogenate was used for the biochemical estimations of lipid peroxidation, glutathione (GSH) and superoxide dismutase (SOD). Results: Ischemia followed by reperfusion led to a significant increase in tissue lipid peroxidation and a decrease in GSH and SOD levels (Group 3). However, in Groups 4, 5 and 6, where the rats were pretreated with vitamin C or E or a combination of both, there was a decrease in lipid peroxidation, and an increase in GSH and SOD levels. Though a decrease in lipid peroxidation was observed in all three vitamin-pretreated groups, it was not as low as in the normal control group. There were no statistically significant differences among the three vitaminpretreated groups. Conclusion: Both antioxidants, singly and in combination, showed equal beneficial effects in reducing renal injury.