Combined but not single administration of vitamin C and l-carnitine ameliorates cisplatin-induced gastric mucosa damage in male rats.

Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions that pose significant and distressing clinical symptoms. Therefore, this study investigated the effects of vitamin C and (or) l-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into 6 groups (n = 5). The control group received distilled water, while the treatment groups received cisplatin alone (CIP), or cisplatin with vitamin C, l-carnitine, or their combination. Cisplatin caused disruption of the gastric mucosa histoarchitecture and altered the mucus barrier function. Moreover, the stomach tissue of the CIP-treated group showed increased levels of oxidative stress markers (malondialdehyde and H2O2) and decreased activities of antioxidant (superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase) and non-antioxidant (reduced glutathione) enzymes. These deleterious events were accompanied with significant increases in pro-inflammatory cytokines and inflammatory infiltration markers, myeloperoxidase and inducible nitric oxide synthase. However, the administration of both vitamin C and l-carnitine, and not either of the two showed additive effects in attenuating the adverse effects of cisplatin. The histological results agreed with the biochemical assays. The study concluded that the combined administration of vitamin C and l-carnitine, but not the single therapy, could prevent the adverse effects of cisplatin on gastric tissue.

Protective Effect of Kolaviron on Cyclophosphamide-Induced Cardiac Toxicity in Rats.

BACKGROUND: Cyclophosphamide (CP) is a nitrogen mustard alkylating drug used for the treatment of chronic and acute malignant lymphomas, myeloma, leukemia, neuroblastoma, adenocarcinoma, retinoblastoma, breast carcinoma, and immunosuppressive therapy. Despite its vast therapeutic uses, it is known to cause severe cardiac toxicity. Kolaviron (KV), a Garcinia kola seed extract containing a mixture of flavonoids, is reputed for its antioxidant and membrane stabilizing properties. OBJECTIVE: This study investigated the protective effect of KV on CP-induced cardiotoxicity in rats. METHODS: Thirty rats were used, and they were divided into 6 groups of 5 rats each. Group I received 2 mL/kg propylene glycol orally for 14 days; group II received CP (50 mg/kg/d, intraperitoneally [i.p.]) for 3 days; groups III and IV received 200 and 400 mg/kg/d KV, respectively, orally for 14 days and groups V and VI were pretreated with 200 and 400 mg/kg/d KV, respectively, orally for 14 days followed by CP (50 mg/kg/d, i.p.) for 3 days. RESULTS: CP treatment resulted in a significantly lower food consumption and body weight in rats. The lactate dehydrogenase and creatine kinase enzymes in cardiac tissues of rats treated with CP were significantly higher. In cardiac tissues, 3-day doses of CP resulted in significantly higher heart weight, cardiac troponin I, myeloperoxidase, malondialdehyde, hydrogen peroxide and lower superoxide dismutase, catalase, glutathione peroxidase activities, and reduced glutathione levels. Histological examination of cardiac tissues showed sign of necrosis of myocardium after CP treatment. However, administration of KV at 200 and 400 mg/kg for 14 days prior to CP treatment, increase food consumption, body weight, and attenuates the biochemical and histological changes induced by CP. CONCLUSIONS: These results revealed that KV attenuates CP-induced cardiotoxicity by inhibiting oxidative stress and preserving the activity of antioxidant enzymes.

Combined Administration of l-Carnitine and Ascorbic Acid Ameliorates Cisplatin-Induced Nephrotoxicity in Rats.

OBJECTIVES: Cisplatin (CIS) is an effective antitumor drug. However, its clinical use is limited due to nephrotoxicity. l-Carnitine and vitamin C are both natural antioxidant that can be obtained from diets. This study investigated the effects of l-carnitine and/or vitamin C in rats against cisplatin-induced nephrotoxicity. METHODS: Twenty-five male Wistar rats were divided into 5 groups of 5 rats each. Group 1, normal control. Group 2, positive control, received cisplatin (10 mg/kg/day intraperitoneally [i.p.]) for 3 days. Groups 3, 4, and 5 received cisplatin for 3 days and thereafter l-carnitine (50 mg/kg/day), vitamin C (100 mg/kg/day), or their combination, respectively, for 28 days. At the end of the study, a biochemical study was carried out in which nephrotoxicity markers, electrolytes, hematological indices, oxidative stress biomarkers, and renal histopathological alterations were evaluated. RESULTS: CIS-treated rats developed significant polyuria, increase in the plasma levels of creatinine, urea, and inorganic phosphate (Pi), alteration in hematological parameters, and decrease in plasma levels of Na+, Cl-, K+, Ca2+, and Mg2+. Measurements of 24-hour urine output demonstrated markedly decreased creatinine and urea and increased Na+, Cl-, K+, Ca2+, and Mg2+ levels in the CIS-treated group, whereas Pi levels were not changed. It also caused significantly decreased catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) levels in the rats' kidneys. Histopathological scores revealed renal tubular damage in CIS-treated rats. However, l-carnitine, vitamin C, or their combination significantly attenuated the alterations caused by CIS in the plasma and kidneys of the rats. CONCLUSION: l-Carnitine and vitamin C administration ameliorated CIS-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.