This study was conducted to investigate the protective effects of sildenafil citrate on testicular injury after testis torsion/detorsion (T/D) in rats. Forty adult male Wistar rats were randomly allocated into four equal groups of ten rats each. Group 1 (Sham-operated); Group 2 (torsion for 2 hours and detorsion for 2 hours); Group 3, (torsion for 2 hours, sildenafil injection and detorsion for 2 hours), and Group 4 (sildenafil injection, torsion for 2 hours and detorsion for 2 hours).The levels of lipid peroxidation (P<0.001) and nitric oxide (P < 0.01) were significantly increased in in the testis of group 2 rats. Testicular reduced glutathione and serum inhibin B levels were decreased significantly (P<0.001) after T/D. Administration of sildenafil either before or after torsion prevented the increase in lipid peroxidation and nitric oxide, and alleviated glutathione and inhibin B levels. Sildenafil also prevented ischemia/reperfusion cellular damage and histological alterations in testicular tissue. These results suggest that treatment with sildenafil citrate 2 hours before or after torsion could induce protective effects against ischemia/reperfusion injury.

Introduction: The high levels of angiotensin II (Ang II) can modify the vascular tone, enhance vascular smooth muscle cells (VSMCs) proliferation and hypertrophy and increase the inflammatory cellular infiltration into the vessel wall. The old herbal nonpharmacological agent, Hibiscus (HS) sabdariffa L has multiple cardioprotective impacts; thus, we investigated the role of HS extract in amelioration of renovascular hypertension (RVH)-induced aortic remodeling.Materials and methods: Thirty-five rats (7/group) were randomly allocated into 5 groups; group: I: Control-sham group, and RVH groups; II, III, IV, and V. The rats in RVH groups were subjected to the modified Goldblatt two-kidneys, one clip (2K1C) for induction of hypertension. In group: II, the rats were left untreated whereas in group III, IV, and V: RVH-rats were treated for 6 weeks with low dose hibiscus (LDH), medium dose hibiscus (MDH), and high dose hibiscus (HDH) respectively.Results: We found that the augmented pro-contractile response of the aortic rings was ameliorated secondary to the in-vivo treatment with HS dose dependently. The cyclophilin A (CyPA) protein levels positively correlated with the vascular adhesion molecule-1 (VCAM-1) and ERK1/2, which, in turn, contribute to the reactive oxygen species (ROS) production. Daily HS intake modified aortic renovation by enhancing the antioxidant capacity, restraining hypertrophy and fibrosis, downregulation of the metastasis associated lung adenocarcinoma transcript (MALAT1), and cyclophilin A (CyPA)/ERK1/2 levels.Discussion: Adding to the multiple beneficial effects, HS aqueous extract was able to inhibit vascular smooth muscle cell proliferation induced by 2K1C model. Thus, adding more privilege for the utilization of the traditional herbal extracts to attenuate RVH-induced aortopathy.

Background: Parkinson's disease (PD) is the most common age-related motor neurodegenerative disease. Current therapeutic modalities for PD are directed at controlling the motor symptoms to slow disease progression, while no exact therapy exists to repair the immient neuronal damage. Despite the involvement of exosomes in the pathogenesis of PD, they serve as a promising therapeutic tool. Exosomes can restore the homeostasis of oxidative stress, neuro-inflammation, and cell apoptosis. Although H2S is involved in the pathogenesis of PD, it has antioxidant, anti-inflammatory and anti-apoptotic neuroprotective effects, giving hope for the role of this gaseous molecule in PD therapy. Objective: We aimed to evaluate the therapeutic effect of exosomes and/ or H2S-donor (NaHS) on PD, through modulation of PI3K/AKT signaling pathway, and to compare their combined effect with the standard treatment, L-DOPA. Methods: This study was conducted on forty-eight female white albino rats divided equally into 6 groups: control group, Parkinson group induced by 6-hydroxydopamine (6-OHDA), 3 Parkinson groups treated with either L-DOPA, exosomes, or H2S-donor (NaHS), and Parkinson group treated with both exosomes and NaHS. The following parameters were assessed in the rat brain tissues: gene expression of Nrf2, Keap1, α-synuclein, and miRNA-141, protein levels of PI3K, AKT, Dopamine, TNF-α and caspase-3. GSH and MDA levels were also measured. In addition, behavioral function tests and histo-pathological examination of rat brain tissues were also performed. Results: In the Parkinson group, there was a significant deficit in behavioral functions, along with down-regulation of the Nrf2 gene and its downstream antioxidant GSH, and increased levels of the lipid peroxidation biomarker MDA. Also, there was increased neuro-inflammation as evidenced by increased levels of TNF-α with decreased levels of the neurotransmitter Dopamine. Moreover, there was increased gene expression of Keap-1, miRNA-141, and αsynuclein associated with decreased levels of AKT, PI3K and increased caspase-3 levels. On the other hand, all treated groups, especially the combined exosomes and H2S donor-treated group, significantly reversed the deteriorating impacts of 6-OHDA on rat brains, as evidenced by the improvement of the behavioral dysfunction and the histopathological picture, which agrees with the biochemical and molecular findings of PI3K/AKT signaling pathway. Conclusion: These data suggest that combined exosomes and H2S-donor could be considered as a potential and effective line for treating PD.