Veterinary Research Forum

Abstract Doxorubicin (DOX), as a potent anti-cancer agent, exerts side effects in vital organs. Various chemical compounds with tissue protective properties are used to prevent the side effects of DOX. This study was planned to investigate the effects of histidine (HIS) and N-acetylcysteine (NAC) ​​on DOX-induced acute kidney injury. The possible mechanisms were followed by determining the histopathological changes of the kidney along with the biochemical alterations of the blood and kidney tissue. Forty-eight rats were divided into eight groups of six animals each to receive normal saline and DOX after alone and combined treatments with HIS and NAC. The DOX at a single dose of 15.00 mg kg^-1 was intraperitoneally injected on day one. The separate and combined intraperitoneally injections of HIS and NAC at a similar dose of 100 mg kg^-1 were began 30 min after DOX administration and continued for seven consecutive days. The DOX increased kidney weight and caused congestion, hemorrhages and degeneration in kidney tissue. It also increased serum urea and creatinine concentrations and kidney tissue levels of malondialdehyde, tumor necrosis factor-alpha and caspase-3, and decreased superoxide dismutase activity in this tissue. Separate and combined treatments with HIS and NAC improved all the above-mentioned effects of DOX. The restoring effects of the combined treatment were more prominent than the effect of amino acids alone. It was concluded that anti-oxidative, anti-inflammatory and anti-apoptotic mechanisms might be related to the tissue protective effects of HIS and NAC against DOX-induced acute renal injury.

Abstract In the present study, we investigated the effects of histidine and vitamin C (alone or in combination) treatments against isoproterenol (a β-adrenergic receptor agonist)-induced acute myocardial infarction in rats. We used propranolol (a β-adrenergic receptor blocker) to compare the results. Rats were given intraperitoneal injections of histidine (40 mg kg^-1) and vitamin C (40 mg kg^-1) alone and combined daily for 21 days. Propranolol (10 mg kg^-1) was orally administered daily for 10 days (from day 11 to day 21). Myocardial infarction was induced by subcutaneous injections of 150 mg kg^-1 of isoproterenol at an interval of 24 hr on days 20 and 21. Blood and tissue samples were taken for histopathological and biochemical evaluations following electrocardiography recording on day 21. Isoproterenol elevated ST segment, increased heart weight, heart rate, serum activities of aspartate transaminase, lactate dehydrogenase, creatine kinase-MB and heart tissue content of malondialdehyde, and decreased R wave amplitude and superoxide dismutase and catalase activities of heart tissue. Necrosis, edema and inflammatory cells infiltration were observed in myocardial tissue sections. Our results indicated that histidine and vitamin C alone, and especially in combination prevent isoproterenol-induced cardiotoxicity and have similar protective effects with propranolol. Cardioprotective effects of histidine and vitamin C may be associated with their ability to reduce free radical-induced toxic effects.

Abstract In this study, the effects of separate and combined intraperitoneal (IP) injections of histidine and dexamethasone were investigated on local inflammation in rats. Local inflammation was induced by subcutaneous (SC) injection of histamine (100 μl, 0.1%) in ventral surface of right hind paw. The thickness of paw was measured at 30 min before and 30, 60, 90, 120, 150 and 180 min after injection of histamine, using a fine caliper. The number of neutrophils in paw tissue sections was counted 3 h after intraplantar (IPL) injection of histamine. The IPL injected histamine elicited an inflammatory response that was characterized by increase of paw thickness and by infiltration of neutrophils in paw tissues. IP injections of histidine at doses of 200 and 400 mg kg-1 and dexamethasone at a dose of 1 mg kg-1 significantly (P < 0.05) decreased both paw thickness and infiltration of neutrophils in paw tissues. In combined treatment, IP injection of histidine (200 mg kg-1) with dexamethasone (1 mg kg-1) produced a more documented response in comparison with histidine and dexamethasone used alone. The results suggested that histidine and dexamethasone have anti-inflammatory activities. Histidine potentiated the anti-inflammatory effect of dexamethasone in histamine-induced local inflammation.