What is the protective effect of preischemic kisspeptin-10 administration against ischemia/reperfusion injury of striatum on mice?

Abstract

Background/aim Kisspeptin is a neuropeptide with a primary role on the onset of puberty and has beneficial effects on ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate the effect of kisspeptin administration on striatal I/R injury in mice. Material and methods Forty adult C57/BL6 mice were randomly divided into four groups: Sham, Kisspeptin, I/R, and I/R + Kisspeptin groups. The groups were administered with either physiological saline (Sham and I/R groups) or kisspeptin (Kisspeptin and I/R + Kisspeptin groups) intraperitoneally 40 min before the operation. A microdialysis probe was placed in the right striatum according to stereotaxic coordinates. During the experimental period, artificial cerebrospinal fluid was passed through the micropump. Then, transient cerebral ischemia was established by compressing both common carotid arteries with an aneurysm clip for 15 min and animals were reperfused for 2 h. Throughout the process of microdialysis (before, during and after I/R period), samples were collected to measure dopamine (DA), noradrenaline (NA), and 3,4-dihydroxyphenylglycine (DHPG) at intervals of 20 min continuously. At the end of the reperfusion period, the animals were decapitated, striatum was dissected, half of the animals were used for oxidative stress analyses (reduced glutathione, glutathione S-transferase (GST), superoxide dismutase (SOD), malondialdehyde (MDA), and the other half were used for histopathology analyses. Results Number of glial cells was significantly increased in kisspeptin-administered groups. DA levels in ischemic animals were decreased by kisspeptin administration (p < 0.0001). NA levels were reduced in animals administered with kisspeptin without I/R injury (p < 0.05). DHPG levels reduced during the reperfusion period in ischemic animals (p < 0.05). Kisspeptin did not exhibit a significant antioxidant activity in the ischemic animals, while GST and SOD levels were reduced in the I/R + kisspeptin group compared to the kisspeptin group (p < 0.05). Conclusion Our results suggest that kisspeptin may be regulating the neurotransmitter release and metabolism, as well as inflammatory response in brain upon I/R injury.

Kisspeptin-10 Improves Testicular Redox Status but Does Not Alter the Unfolded Protein Response (UPR) That Is Downregulated by Hypothyroidism in a Rat Model

“…Although Kp10 did not change the low expression of these genes caused by hypothyroidism, a significant increase in the immunostaining of SOD1 and GPX1/2 was observed after treatment, highlighting their antioxidant effects in tests on hypothyroid rats. This corroborates the findings of previous studies in which the administration of Kp10 increased antioxidant defense at the maternal-fetal interface of hypothyroid rats [27], as also observed in models of ovarian and uterine [33], testicular [34], cardiac [35] and brain dysfunctions in mice [36]. The increase in antioxidant defense caused by Kp10 in the present study may be involved in the improvement of testicular morphology and steroidogenesis and sperm quality observed in hypothyroid rats after treatment with Kp10 [5].…”

“…Studies have been conducted to evaluate the potential of substances to reduce the effects of OS and/or ER stress in the reproductive tract [27,28]. In this regard, kisspeptin, which control the hypothalamic release of gonadotropin-releasing hormone (GnRH) [29,30] and has local action in the testes [31,32], has been recognized for its antioxidant effects in models of ovarian and uterine, [33] testicular, [34], cardiac [35] and brain disease in mice [36]. In addition, in vitro overexpression of kisspeptin in human granulosa cells increased proliferation, inhibited apoptosis, suppressed ROS generation, reduced malondialdehyde (MDA) levels, and increased levels of antioxidant factors [37].…”