Browsing by Author "Shishir Kumar Patel"

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Effect of standardized extract of Bacopa monnieri (CDRI-08) on testicular functions in adult male mice
(Elsevier Ireland Ltd, 2017) Shishir Kumar Patel; Shilpi Singh; Hemant Kumar Singh; Shio Kumar Singh
Ethnopharmacological relevance Bacopa monnieri (BM) has been used in India since the time of Rig-Veda for augmentation of learning, memory, brain health etc. Aim of the study The memory augmenting effect of BM is well documented. CDRI-08 is a standardized extract of Bacopa monnieri, but its effect on the male reproductive health has not been investigated. Therefore, the aim of the present study was to examine the effect of CDRI-08 administration on the male reproductive organs with special emphasis on testis in adult mice. Materials and methods CDRI-08, containing at least 55% bacosides (the major constituent of BM), was investigated for its effect on testicular functions in adult Parkes (P) mice. A suspension of CDRI-08 was orally administered in doses of 40 and 80 mg kg−1 body weight day−1 for 28 days and various male reproductive end points were evaluated. Results Compared to control, CDRI-08 treatment caused a significant increase (p<0.05) in spermatogenic cell density (germinal epithelial height: control, 55.03±4.22 vs 40 mg, 67.15±2.65 and 80 mg, 69.93±3.76; and tubular diameter: control, 206.55±2.62 vs 80 mg, 253.23±12.19), PCNA index (control, 59.85±2.09 vs 40 mg, 82.17±1.56 and 80 mg, 84.05±3.51) and in steroidogenic indices in the testis, and in sperm viability (control, 0.67±0.010 vs 80 mg, 0.80±0.04) in cauda epididymidis of the treated mice. On the other hand, however, the same treatment caused a significant decrease (p<0.05) in abnormal sperm morphology (control, 21.72±1.06 vs 40 mg, 10.63±1.50 and 80 mg, 15.86±0.87) in cauda epididymidis, and in lipid peroxidation level in testis of the treated mice compared to controls. Conclusion The results suggest that treatment with CDRI-08 extract improves sperm quality, and spermatogenic cell density and steroidogenic indices in the testis of P mice. © 2016 Elsevier Ireland Ltd
Long-term exposure of 2450 MHz electromagnetic radiation induces stress and anxiety like behavior in rats
(Elsevier Ltd, 2019) Sukesh Kumar Gupta; Shishir Kumar Patel; Munendra Singh Tomar; Shio Kumar Singh; Manoj Kumar Mesharam; Sairam Krishnamurthy
Long term exposure of electromagnetic radiations (EMR) from cell phones and Wi-Fi hold greater propensity to cause anxiety disorders. However, the studies investigating the effects of repeated exposure of EMR are limited. Therefore, we investigated the effects of repeated exposure of discrete frequencies of EMR in experimental animals. Male rats were exposed to EMR (900, 1800 and 2450 MHz) for 28 (1 h/day) days. Long term exposure of EMR (2450 MHz) induced anxiety like behavior. It deregulated the hypothalamic pituitary adrenal (HPA) axis in rats as observed by increase in plasma corticosterone levels apart from decreased corticotrophin releasing hormone-2 (CRH-2) and Glucocorticoid receptor (GR) expression in amygdala. Further, it impaired mitochondrial function and integrity. The expression of Bcl 2 showed significant decrease while Bax and ratio of Bax: Bcl 2 were increased in the mitochondria and vice versa in cytoplasm indicating altered regulation of apoptosis. EMR exposure caused release of cytochrome-c and expression of caspase-9 ensuing activation of apoptotic cell death. Additional set of experiments performed to estimate the pattern of cell death showed necrotic and apoptotic amygdalar cell death after EMR exposure. Histopathological studies also revealed a significant decrease in neuronal cells in amygdala. The above findings indicate that long-term exposure of EMR radiation (2450 MHz) acts as a stressor and induces anxiety-like behaviors with concomitant pathophysiological changes in EMR subjected rats. © 2019
Ontogeny of QRFP and its receptor expression in mouse testis during post-natal development
(Elsevier B.V., 2019) Shishir Kumar Patel; Shio Kumar Singh
Pyroglutamylated RFamide peptide (QRFP), a neuropeptide, binds to its receptor GPR103 and influences various biological functions. In the present study, expression and localization of QRFP and GPR103 in mouse testis during post-natal development were investigated. The results showed that QRFP and GPR103 and also the isoforms of the receptor, viz. GPR103A and GPR103B were expressed in mouse testis during post-natal development. Expression of QRFP and its receptor was high during the early periods of post-natal development. Immunohistochemical study demonstrated the localization of QRFP and GPR103 in both interstitial and tubular compartments of the testis throughout post-natal development. A shift in the germ cell types expressing QRFP and its receptor along the course of testicular development and also a prominent immunoreactivity of QRFP in germ cells and of GPR103 in Sertoli cells was observed. Further, the immunoreactivity of QRFP and GPR103 appeared to be stage-specific in spermatogenetically active testis. Besides in intercellular spaces, localization of QRFP was also noticed in nuclei of germ cells. In conclusion, the present results suggest potential involvement of QRFP system in the development, proliferation and differentiation of testicular cells, possibly by regulating the energy requirement for these processes. © 2018 Elsevier B.V.
Pyroglutamylated RFamide peptide (QRFP): Role in early testicular development in relation to Sertoli cell maturation in prepubertal mice
(Churchill Livingstone, 2022) Shishir Kumar Patel; Shio Kumar Singh
QRFP, an orexigenic neuropeptide, binds to its cognate receptor GPR103 and regulates various biological functions. We have recently shown that QRFP and its receptor are present in mice testes and that their expression is high during early postnatal period. The present study aimed to investigate the effect of sustained high level of QRFP on Sertoli cells proliferation and differentiation and to relate these events with germ cell differentiation and lumen formation in the seminiferous tubules in mice testes during prepubertal period. QRFP was injected intraperitoneally to male mice from postnatal day 5 to 16. Morphometric analysis and various markers related to Sertoli cell maturation (WT1, p27kip1, AMH, AR and CYP19A1) and germ cell proliferation and differentiation (PCNA, GDNF and c-Kit) were evaluated. QRFP administration caused an early lumen formation in the seminiferous tubules in testis of treated mice. Further, there was a significant increase in p27kip1 expression and a marked decrease in AMH expression in QRFP-treated mice compared to controls. However, no appreciable change was noted in AR expression in treated mice. QRFP treatment also caused an increase in c-Kit expression in treated mice compared to controls, suggesting an accelerated spermatogonial differentiation in testis of QRFP-treated mice. Taken together, the present results suggest that the prolonged high level of QRFP increases Sertoli cell maturation, which, in turn, plays a contributory role in increasing the pace of germ cell differentiation and formation of lumen in the seminiferous tubules. © 2021 Elsevier Ltd
Role of pyroglutamylated RFamide peptide43 in germ cell dynamics in mice testes in relation to energy metabolism
(Elsevier B.V., 2020) Shishir Kumar Patel; Shio Kumar Singh
QRFP is a neuropeptide that regulates glucose homeostasis and increases insulin sensitivity in tissues. We have previously shown that QRFP and its receptor (GPR103) are predominantly expressed in germ cells and Sertoli cells, respectively, in mice testes. In the present study, we report that QRFP caused an increase in PCNA and a decrease in p27Kip1 expressions in the testis under both in vivo and ex vivo conditions. Besides, via an in vivo study, cell cycle analysis by FACS showed an increase in 2C cells and a decrease in 1C cells. QRFP also induced expression of GDNF and phosphorylation of Akt and ERK-1/2. Together these results suggest that QRFP has a proliferative effect on germ cells in mice testes, since it caused a proportional increase in the mitotic activity and the number of spermatogonial cells. Further, observations of increased expressions of STAT-3 and Neurog3 in treated mice suggest that QRFP treatment regulates priming of undifferentiated spermatogonia to undergo differentiation, while a decrease in c-Kit expression indicate that spermatogonia at this time point are in an undifferentiated state. In addition, QRFP administration also caused an increase in intratesticular levels of glucose and lactate, and in LDH activity accompanied by increased expressions of GLUT-3 and LDH-C in the testis. Also, the phosphorylation of IR-β and expressions of p-Akt and p-mTOR were increased under ex vivo conditions in testicular tissue. In conclusion, our findings suggest that QRFP treatment caused proliferation of germ cells independently from the hypothalamic-pituitary axis via regulation of testicular energy metabolism. © 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM)
Standardized extract of Bacopa monnieri (CDRI-08): Effect on germ cell dynamics and possible mechanisms of its beneficial action on spermatogenesis and sperm quality in male mice
(Elsevier B.V., 2017) Shishir Kumar Patel; Shilpi Singh; Shio Kumar Singh
Bacopa monnieri (BM) is used in traditional medicine as nerve tonic. We have recently shown that CDRI-08, a standardized extract of BM, improves testicular functions and epididymal sperm quality in Parkes (P) mice. The aim of the present study was to investigate the effect of CDRI-08 on germ cell dynamics and mechanisms of its action on spermatogenesis and sperm quality in P mice, and to determine the chemical profile of the extract. CDRI-08 (40 and 80 mg/kg body weight) was orally administered to male mice for 28 days. Germ cell dynamics, oxidative stress parameters in testis and sperm, and expressions of nuclear factor-erythroid-2-related factor-2 (Nrf2), phosphorylated protein kinase B (p-Akt) and upstream kinases in mitogen-activated protein kinase (MAPK) pathway namely MAP2K1, MAP2K2 and MKK4 in the testis were evaluated. The treatment potentiated germ cell dynamics and improved sperm quality by enhancing antioxidant enzymes activities. The beneficial effects of CDRI-08 in the testis involve p-Akt-mediated activation of Nrf2, thereby enhancing antioxidant enzymes activities; upregulation of MAP2K1 and MAP2K2 and suppression of MKK4 are also implicated in this action. A total of 26 phytocomponents were identified in CDRI-08 by GC-MS. The results suggest that CDRI-08 also may prove useful in improving reproductive health in males. © 2017 Elsevier Inc.