Effects of histidine and N-acetylcysteine on acute kidney injury induced by doxorubicin in rats: roles of anti-oxidative, anti-inflammatory and anti-apoptotic mechanisms
Volume 16, Issue 9, September 2025, Pages 507-514
Sanam Mansouri, Amir Abbas Farshid, Esmaeal Tamaddonfard
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.
Protective effects of garlic aquous extract (Allium sativum), vitamin E, and N-acetylcysteine on reproductive quality of male rats exposed to lead
Volume 4, Issue 4, December 2013, Pages 251-257
Reza Asadpour, Mehdi Azari, Marzie Hejazi, Hossein Tayefi, Neda Zaboli
Abstract The objective of present study was to investigate the effects of aqueous garlic extracts, vitamin E and N-acetylcysteine on lead-induced lipid peroxidation, changes in antioxidant defense system and semen quality in the rat testes. Twenty-five male rats were divided into five groups. Animals within different treatment groups were maintained on their respective diets for 35 days as follows: group 1 rats served as control and received water and standard pellets as food ad libitum; group 2 received lead acetate by gavage (1000 ppm); group 3 was treated with A. sativum extract (400 mg kg-1, by gavage) plus lead acetate (1000 ppm); group 4 was treated orally with vitamin E (300 mg of alpha-tocopherol per kg of chow) plus lead acetate (1000 ppm); group 5 was treated orally with N-acetylcysteine (800 ppm)plus lead acetate (1000 ppm). The weights of testes, epididymis, epididymal sperm count, viable and motile sperms decreased significantly (p < 0.05) in lead-exposed rats. However treatment with vitamin E and aqueous garlic extract resulted in a significant (p < 0.05) increase in sperm motility and viability. Exposure to lead acetate significantly increased malondialdehyde (MDA) level with a significant decrease in the superoxide dismutase (SOD) activities in the testes of rats while co-administration of vitamin E and lead caused a significant (p < 0.05) decrease in MDA concentration compared with lead-exposed group. These results suggest that both vitamin E and in to a lesser extent aqueous garlic extract have a potent antioxidant protection in the testes of rat against the lead-induced oxidative stress.
