Background: This research aimed to evaluate the protective effects of methanolic extract of Zataria Multiflora Boiss (Z. Multiflora) against hepatic damage induced by cisplatin in male Wistar rats. Methods: Hepatotoxicity was induced in Wistar male rats by a single intraperitoneal administration of cisplatin, 7 g/ kg body weight. A methanolic extract of Z. Multiflora was administered orally at doses of 50 mg/ kg, 100 mg/ kg, 200 mg/ kg and 400 mg/ kg body weight daily for seven days after being cisplatin-induced. The study included the histopathological examination of the liver sections. The activity of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were evaluated as markers of liver damage. The superoxide dismutase (SOD), the activity of Catalase (CAT), and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) and nitric oxide (NO) content in serum were measured as an oxidative stress factor. Results: The results showed that rat treated with cisplatin resulted in a significant increase in serum activity, AST, ALT and ALP in treated mice. Management with Z. Multiflora reduced the business of these enzymes to nearly normal levels. In parallel with these changes, this extract reduced cisplatin-induced oxidative stress by inhibiting lipid peroxidation and protein carbonylation, and restoring the antioxidant enzyme (SOD, CAT, and GSH-Px) and elevation of the glutathione level. Conclusion: Biochemical and histological observations showed the hepatoprotective effect was found in a dose-dependent manner in Z. Multiflora methanolic extract. This protective effect can be attributed to the antioxidant compounds.

Hepatoprotective effect of Zataria Multiflora Boisson cisplatin-induced oxidative stress in male rat.

5-Fluorouracil is one of the most widely used chemotherapeutic agents in case of hepatic neoplasms. The object of this study was to determine the effectiveness of vitamin C in alleviating 5-fluorouracil-induced hepatotoxicity in male mice. Thirty male albino mice were divided equally into 3 groups, each of 10 animals; group 1, mice received normal saline solution (control group); group 2, mice received 5-fluorouracil 80 mg/kg b.wt./day intraperitoneally for 4 weeks (5-fluorouracil group); group 3, mice received 5-fluorouracil 80 mg/kg b.wt./day for 4 weeks with daily injection of vitamin C (12 mg/kg b.wt./day) for 4 weeks. Animals of all groups were sacrificed and tissue samples from the liver were taken and processed for both light and electron microscopical examination. Light microscopic observations revealed that administration of 5-fluorouracil causes variable signs of hepatotoxicity which are represented by focal areas of liver cell necrosis with distortion of normal hepatic architecture; the hepatocytes showed vacuolated cytoplasm and pyknotic nuclei together with inflammatory cell infiltration. Dilated, congested hepatic sinusoids with active kupffer cells were also seen. Ultrastructure examination confirmed the light microscopic findings and demonstrated vacuolated hepatocytes cytoplasm, dilated endoplasmic reticulum, increased lysosomes, electron-dense mitochondria and pyknotic nuclei. Treatment with vitamin C with 5-fluorouracil attenuated 5-fluorouracil-induced hepatotoxicity and reverted the abnormal structural changes to near normal. In conclusion, these results suggest that vitamin C has a protective potential in ameliorating 5-fluorouracil-induced hepatotoxicity.

Ameliorative effect of vitamin C against 5-fuorouracil-induced hepatotoxicity in mice: A light and electron microscope study

The present study was intended to determine the histological changes induced by Cytarabine drug on the structure of rabbit's livers and the protective effects of vitamin E on these histological changes. The treated group with daily intraperitoneal dose of (50 mg/kg body weight) of Cytarabine alone, showed a massive histological change represented by infiltration of mononuclear inflammatory cells, epithelioid cell and Kupffer's cells in hepatic tissue. Fibrosis in portal area, congestion of blood vessels as well as hyperplasia of bile canaliculi and coagulative necrosis of hepatocytes were also noticed in other sections. While the group that received protective (800 IU of vitamin E) prior to each Cytarabine injection, showed a considerable histological improvement than the group received Cytarabine alone, as the histological sections of this group showed a nearly normal histological architecture of the liver that represented by normal arrangement of hepatic cords, no fibrosis no congested blood vessels were seen. though distension of hepatic sinusoids and coagulative necrosis of some hepatocytes were still observed. The present study suggested that vitamin E is an effective chemo-protective agent against hepatotoxicity when used as a protective agent prior to Cytarabine drug taken.

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The histological changes induced by cytarabine on rabbits kidneys (with and without vitamin E administration)

The present study was designed to investigate the ameliorative effect of vitamin C administration on serum alanine aminotransferase (ALT),aspartate aminotransferase(AST),Urea, Creatinine, Alphafetoprotein(AFP), Carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 199), in addition to tumor necrosis factor alpha (TNF-α) , Cytochromep4502E1 and Caspase-9 gene expression in colon cancer induced by 1,2-dimethylhydrazine (DMH)in rats. Forty white female albino rats were divided into four equal groups (10 each). Group I(control group):received no drugs. Group II:(DMH group): rats injected subcutaneously with DMH (35 mg/kg body weight),twice a week for 5 consecutive weeks for colon cancer induction. Group III:(protective group): rats administrated vit C(200 mg kg-1 b. wt) orally and for 4 weeks before DMH injection and continued with vit C administration daily till the end of the experiment .Group IV:(treatment group):rats injected subcutaneously with DMH then administrated Vit C for 6 weeks till the end of the experiment. Blood and colon tissue samples were collected from all animal groups at the end of the experiment. The obtained results showed that DMH injection to rats significantly increased serum(ALT, AST, Urea, Creatinine, AFP, CEA, CA 19-9) and colon tissue TNF-α and CYP2E1while colon tissue caspase-9 gene wassignificantly decreasedwhen compared to control.Administration of Vit C significantly decreased serum (ALT, AST, Urea, Creatinine, AFP, CEA, CA 19-9) in addition to TNF-α and CYP2E1in colon tissue. How every, caspase-9 gene expression showed a significant increase. Histopathological examination of colon tissue edesquamation of the colon epithelium with heavy leukocytic infiltrationin DMH group. While administration of vitamin C in colon cancer induced rats showed mild destruction of the lining epithelium with mild leukocytic infiltration in addition to mild malignancy of epithelium when compared to DMH group. These results indicated the protective effect of Vit C against DMH induced colon cancer.

https://bvmj.journals.ekb.eg/article_54257_988a3ab38cf59279fb15e53f022c8fde.pdf

The ameliorative effect of Vitamin C in experimentally induced colon cancer in rats

Infertility is a major concern for young men of reproductive age under-going chemotherapy. Unfortunately, chemotherapeutic treatment for neoplastic diseases commonly impairs fertility either temporally or permanently. In general, chemotherapeutic agents in cancer treatments target all rapidly growing healthy cells, such as those of reproductive system in addition to tumor tissues and it therefore results in impairment of spermatogenesis leading to abnormalities in sperm morphology in cancer survivors. Consequently, antioxidants have been shown to protect nonmalignant cells and organs against damage by chemotherapeutic agents. Hence the present study was designed to evaluate the possible ameliorative role of curcumin or vitamin C alone and their combination in alleviating the toxicity of cisplatin on sperm morphology when given to normal albino rats. The results of the present investigation concluded that the combination between curcumin and vitamin C in cisplatin treatment afforded the best ameliorative effect on cisplatin induced sperm shape abnormalities. This may be due to the synergistic effect between curcumin and vitamin C as both of them have antioxidant properties which in turn lead to repairing of sperm abnormalities.

Protective effect of curcumin and vitamin C each alone and in combination on cisplatin-induced sperm abnormalities in male albino rats

Cisplatin drug is one of platinum compounds and it is in common use world wide for the treatment of a variety of human neoplasms. However in high doses it can produce undesirable toxic side effects on liver, so in this study we investigated whether vitamin C has protective effect on hepatotoxicity induced by cisplatin or not. Three equal-sized groups (six rats each) of adult male albino rats were used as a)control group b)recipient of cisplatin or c)recipient of vitamin C, 24 hrs before cisplatin injection. Histological examination of livers were carried out using light microscopy. Results showed that cisplatin produced pathological changes manifested as severe fatty changes, congestion and dilatation of portal blood vessels and central veins, dilatation and congestion of sinusoids, with multiple necrotic foci and apoptotic cells, while prior administration of vitamin C produced amelioration of the pathological changes induced by cisplatin.

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Ahmad H. Al-Jawary

Papers

Effect of Vitamin C on the Hepatotoxicity Induced by Cisplatin in Rats