Abstract

Methotrexate (MT) is a broadly used chemotherapeutic drug however its clinical use is confronted with several forms of toxicities containing testicular damage. The current study assessed the ameliorative effects of morin on MT-induced testicular damage with the investigation of its mechanism and the potential involvement of oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in such protection. The animals were divided into 5 distinct groups (7 rats in each group). Group 1 was control group, group 2 received MT-only (20mg/kg bw), group 3 received orally morin-only (100mg/kg bw), group 4 received MT (20mg/kg bw) + morin (50mg/kg bw) and group 5 received MT (20mg/kg bw) + morin (100mg/kg). In this study, morin was administered orally for 10 days, while MT was administered intraperitoneally on the 5th day. MT intoxication was linked with augmented MDA while decreased GSH levels, the enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase and mRNA levels of HO-1 and Nrf2 in the testis tissues. MT injection caused inflammation in the testicular tissue via up-regulation of MAPK14, NFκB, TNF-α and IL-1β. MT application also caused apoptosis and endoplasmic reticulum stress in the testis tissue via increasing mRNA transcript levels of Bax, caspase-3, PERK, IRE1, ATF-6, GRP78 and down-regulation of Bcl-2. Treatment with morin at a dose of 50 and 100mg/kg considerably mitigated oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress in the testicular tissue indicating that testicular damage related to MT toxicity could be modulated by morin administration.

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