ORIGINAL ARTICLE Melatonin prevents dexamethasone-induced testicular oxidative stress and germ cell apoptosis in golden hamster, Mesocricetus auratus Arun Mukherjee, Chandana Haldar & Dipanshu Kumar Vishwas Department of Zoology, Pineal Research Laboratory, Banaras Hindu University, Varanasi 221005, India Keywords Dexamethasone—golden hamster—melato- nin—testicular damage Correspondence Prof. Chandana Haldar, Department of Zool- ogy, Pineal Research Laboratory, Banaras Hindu University, Varanasi 221005, India. Tel.: +91 542 6702535 Ext. 209; Fax: +91 542 2368174; E-mail: chaldar2001@yahoo.com Accepted: August 05, 2014 doi: 10.1111/and.12357 Summary This study investigated the protective effect of melatonin on dexamethasone (Dex), an extensively used anti-inflammatory and immunosuppressive synthetic glucocorticoid, induced testicular oxidative stress and germ cell apoptosis in golden hamster. Hamsters were randomly divided into four groups (n = 7): group I – control; group II – melatonin treated (10 mg kg À1 day À1 ); group III – Dex treated (7 mg kg À1 day À1 ) and group IV – combination of Dex and melatonin. All the injections were administered intraperitoneally for seven con- secutive days. The histopathological changes, specific biochemical markers, including antioxidative enzymes, plasma melatonin level and the markers for germ cell apoptosis were evaluated. Dex administration decreased antioxidant enzyme activities (SOD, CAT, GSH-P X ), plasma melatonin level and melatonin receptor (MT1) expression with a concomitant increase in lipid peroxidation (TBARS) and altered testicular histopathology which might culminate into increased germ cell apoptosis as evident from increased Bax/Bcl-2 ratio and caspase-3 expression. However, melatonin pre-treatment enhanced enzyme activities for SOD, CAT, GSH-P X with a simultaneous decrease in Bax/Bcl-2 ratio and caspase-3 expression. Our findings clearly suggest that melatonin improved defence against Dex-induced testicular oxidative stress and prevented germ cell apoptosis, suggesting a novel combination therapeutic approach for management of male reproductive health. Introduction Glucocorticoids are multitasking molecules (Julia, 2006) that influence almost all physiological functions including reproduction (Saplosky et al., 2000). Dex, a commercially available synthetic glucocorticoid, acts primarily as a potent anti-inflammatory (Barnes, 1998) and immunosuppressive (Franchimont, 2004) drug in clinical conditions namely chronic asthma (Barnes, 1998), rheumatoid arthritis (Ki- rwan, 1995; Laan et al., 1999), autoimmune diseases (Chat- ham & Kimberly, 2001) and prevention of graft rejection (Almawi et al., 1998). Exposure to glucocorticoid leads to a variety of unwanted physiological consequences including induction of oxidative stress by enhanced reactive oxygen species (ROS) production in many tissues and organs including vascular endothelial cells (Iuchi et al., 2003) and neural stem cells (Mutsaers & Tofighi, 2012). Administra- tion of glucocorticoid induces apoptosis in testicular germ cells (Yazawa et al., 2000) and Leydig cells (Gao et al., 2002) in a dose-dependent manner (Orazizadeh et al., 2010) and is mediated through glucocorticoid receptor (Yazawa et al., 2000). However, the cellular and molecular mechanisms involved in Dex induced oxidative injury in testis is not fully understood. Glucocorticoids are also known to inhibit Leydig cell steroidogenesis by influencing hypothalamo-hypophysial-gonadal (HPG) axis (Dong et al., 2004; Hardy et al., 2005) as well as by enhanced Ley- dig cell apoptosis (Gao et al., 2002). Thus, Dex-induced germ cell apoptosis was regarded to be solely because of androgen deficiency (Woolveridge et al., 1999). Recent findings suggest that exogenous Dex administration causes germ cell apoptosis in both androgen dependent and inde- pendent stages of spermatogenic cycle, and thus, Dex- induced germ cell apoptosis is not absolutely due to hor- monal imbalance (Orazizadeh et al., 2010). The golden hamster (Mesocricetus auratus) is a long-day seasonal breeder and, consequently, being studied for investigating seasonal regulation of reproductive functions © 2014 Blackwell Verlag GmbH 1 Andrologia 2014, xx, 1–12