Protective effect of MOTILIPERM in varicocele-induced oxidative injury in rat testis by activating phosphorylated inositol requiring kinase 1α (p-IRE1α) and phosphorylated c-Jun N-terminal kinase (p-JNK) pathways

Abstract

Context: MOTILIPERM was prepared as a mixture of extracts of three medicinal herbs [roots of Morinda officinalis How (Rubiaceae), outer scales of Allium cepa L. (Liliaceae) and seeds of Cuscuta chinensis Lamark (Convolvulaceae)].Objective: To investigate the role of reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress in a rat model of varicocele and the therapeutic efficacy of MOTILIPERM in this model.Materials and methods: Sixty male rats were divided into five experimental groups: a normal control group (CTR + vehicle), a control group administered MOTILIPERM 200 mg/kg (CTR + M 200), a varicocele-induced control group (VC + vehicle) and two varicocele-induced groups administered MOTILIPERM 100 (VC + M 100) or 200 (VC + M 200) mg/kg for 4 weeks. Testis weights were recorded and serums were assayed for hormone concentrations. Tissues were subjected to semen analysis, histopathology, analyses of ER response protein expression levels and oxidative stress were assessed by measuring ROS, reactive nitrogen species (RNS), malondialdehyde (MDA) level and ratios of total glutathione (GSH)/oxidized GSH (GSSG).Results: MOTILIPERM treatment of varicocele-induced groups significantly increased left testis weight, testosterone level, sperm motility, count and spermatogenic cell density. ER-response protein expression levels were dose-dependently decreased in VC + M 200 group compared with VC + vehicle group. MOTILIPERM treatment also decreased MDA and ROS/RNS level but increased GSH/GSSG ratio.Discussion and conclusions: This study suggests that ROS-related ER stress may play a major role in varicocele-induced infertility and MOTILIPERM, a novel compound targeting ROS-based ER stress, may be therapeutically useful in treatment of varicocele, or as a supplement for the treatment of infertility.

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review

“…A study by Kim et al [13] reported that repetitive cycle of testicular hyperthermia leads to ER stress associated apoptosis of spermatocytes in mouse testis by activation of IRE1-JNK and PERK pathway. In support of these observation, recent study from our lab report varicoceleinduced infertility in rat model by ROS-dependent ER stress in testis [35]. In a study on testicular injury after torsion/detorsion in rat model reported the germ cell apoptosis in testis by upregulate eIF2α and CHOP, which insight the role of ER stress in testicular ischemia/reperfusion injury [45].…”

“…Oxidative stress elicits a reduction-oxidation (redox) imbalance [33]. Alteration of redox homeostasis in ER disturbs ER protein folding and causes ER stress, and accumulation of ROS in the ER and mitochondria [35]. Furthermore, oxidative protein folding in the ER of eukaryotic cells generates ROS as a byproduct and cause oxidative stress [32].…”

Role of Antioxidant Natural Products in Management of Infertility: A Review of Their Medicinal Potential

“…This elucidated the possible usage of this formula to treat male infertility by preventing apoptosis of sperm. MOTILIPERM is a mixture of three natural extracts of Morinda officinalis How, Allium cepa L., and Cuscuta chinensis Lamark, which is used to treat rheumatoid arthritis and impotence [ 94 ]. Soni et al reported that MOTILIPERM (100, 200 mg/kg for 4 weeks) exerted protective effects in varicocele induced SD rats by improving reproductive organ parameters (left testis weight, sperm motility, sperm count, epididymis motility, vas deferens count, epididymis count, spermatogenic cell density, and the percentage of damage of seminiferous tubule).…”

Oxidative stress mediates renal endothelial cell damage in trichloroethylene-sensitized mice

“…ROS are the main marker of oxidative stress, but ROS content was difficult to detect in vivo directly. Malondialdehyde (MDA), an end product of lipid hydroperoxide decomposition, is the most frequently measured index of lipid peroxidation, which can indirectly reflect the ROS content (Soni et al, 2018). The other one is reactive nitric species (RNs).…”