Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats.

OBJECTIVE: Oxidative stress plays an important role in doxorubicin (DOX)-induced toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of this study was to evaluate the decreasing or preventive effect of CAR alone or combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver, and brain of rats. METHODS: Rats were treated with CAR (250 mg kg(-1) day(-1); intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg(-1) α-tocopherol; once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of treatment, rats were injected with a single dose of DOX (30 mg kg(-1), i.p.). Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and oxidative stress parameters in tissues were measured. We also determined thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC), and glutathione levels and antioxidant enzyme activities. RESULTS: DOX resulted in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to decreases in serum cTnI levels and ALT and AST activities. These treatments reduced prooxidant status and ameloriated histopathologic findings in the examined tissues. CONCLUSION: Our results may indicate that CAR alone, especially in combination with Vit E, protect against DOX-induced toxicity in heart, liver, and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and renal markers and restoration of the prooxidant state and amelioration of histopathologic changes.

Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzene sulphonic acid-induced colitis.

Ulcerative colitis (UC) is a multi-factorial inflammatory disease of the colon and rectum. The present study was undertaken to investigate the effect of taurine, an anti-oxidant amino acid, on oxidative stress and the expression of apoptosis-related proteins, pro-apoptotic Bax and anti-apoptotic B cell lymphoma-2 (Bcl-2) in colon tissue in rats with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Rats received taurine (1.5% w/v) in drinking water for 15 days before and 15 days after administration of TNBS solution. Then, colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and Bax and Bcl-2 expression were measured. TNBS-induced colitis caused significantly increased MPO activity and MDA levels and decreased GSH levels in colon tissue compared to controls. Increase in Bax expression and decrease in Bcl-2 expression were detected in colon of rats with TNBS-induced colitis. Taurine treatment was associated with amelioration in macroscopic and microscopic colitis scores, decreased colonic MPO activity and MDA levels and increased GSH levels in TNBS-induced colitis. In addition, taurine reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of rats with TNBS-induced colitis. The results of this study show that taurine administration may exert beneficial effects in UC by decreasing inflammatory reactions, oxidative stress and apoptosis.

Effects of thyroxine replacement on lipid profile and endothelial function after thyroidectomy.

BACKGROUND: Hypothyroidism is a risk factor for atherosclerotic cardiovascular disease. This study investigated the effects of L-thyroxine replacement therapy on lipid profile and endothelial function after thyroidectomy in patients with overt transient non-autoimmune hypothyroidism. METHODS: Twenty-two patients with non-toxic multinodular goitre treated by total or near-total thyroidectomy and 22 healthy individuals matched for age, sex and body mass index were studied. Lipid profile and endothelial function were determined in each patient at the euthyroid phase before thyroidectomy (stage 1), the hypothyroid phase 3 weeks after surgery (stage 2), and the euthyroid phase 3 months (stage 3) and 6 months (stage 4) after the start of thyroxine treatment. RESULTS: The lipid profile and endothelial function deteriorated between stage 1 and stages 2 and 3. Findings at stage 4 were similar to those at stage 1. There was a positive correlation between serum thyroid-stimulating hormone (TSH) and total cholesterol (r(s) = 0.588, P < 0.001), and a negative correlation between serum TSH and flow-mediated arterial dilatation (r(s) = 0.506, P < 0.001). Total cholesterol and TSH were independent determinants of endothelial function. CONCLUSION: A 3-week hypothyroid period after thyroidectomy led to a more atherogenic lipid profile and impaired endothelial function that persisted for at least 3 months.