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Background: Monosodium glutamate is a food additive and flavour enhancer in processed foods and soups that is considered to affect testicular histology. The aim of this research was to investigate the impact of monosodium glutamate (MSG) on testicular structure in rats and explore the potentially protective effects of resveratrol. Materials and methods: Four experimental groups involved in our study contained 10 rats in each. The first group was a control group; in the second group (the resveratrol group) control rats received 20 mg/kg of resveratrol via oral gavage; in the third group (the MSG group) rats received monosodium glutamate (MSG) at a dose of 60 mg/kg body weight daily, via a gastric tube. The fourth group we called the MSG + resveratrol group. Serum levels of testosterone, FSH, and LH were measured. Testicular specimens were prepared for measurement of oxidative stress markers, and gene expression of NLRP3, caspase-3, and GSK-3b. Moreover, paraffin blocks contained testicular tissue used for histological and immunohistochemical examination. Additionally, seminal smears from epididymis were examined. Results: MSG administration adversely affected testosterone production, hormonal levels, and sperm parameters, Histological examination revealed marked testicular degeneration, and oxidative stress assessments indicated an elevated level of MDA, a lipid peroxidation marker, and decreases in SOD and CAT, two antioxidant enzymes. Moreover, MSG induced apoptotic and pyroptotic markers and its gene expressions. Importantly, the administration of resveratrol reversed these detrimental effects of MSG, demonstrating its corrective influence on hypothalamic-pituitary-gonadal axis disruption, the improvement of sperm parameters, the attenuation of oxidative stress, and anti-apoptotic activity and anti-pyroptotic effects. The expression of Ki-67 as a cell proliferation marker further supported the positive response to spermatogenesis dysfunction upon resveratrol treatment. Conclusions: This article sheds light on the protective effect of resveratrol against MSG-induced testicular damage, with an exploration of its mechanistic role. [ABSTRACT FROM AUTHOR]

Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups (n = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly (p < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (p< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly (p < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway. [ABSTRACT FROM AUTHOR]

Our research work examined the potential protection of Stevia rebaudiana extract against monosodium urate crystals (MSU)-induced acute gouty arthritis in a rat model and its possible underlying mechanism. Forty rats were allocated into four groups (n = 10); a control group; an MSU group, whose rats received 0.1 of MSU single intra-articular injection in the ankle joint on the fifth day of the experiment; an MSU + Stevia group, which received 250 mg/kg/day of Stevia extract orally for seven days and MSU crystals on the fifth day; and an MSU + colchicine group, which was administered colchicine at 0.28 mg/kg daily for seven days and MSU crystals on the fifth day. Pretreatment with Stevia extract mitigated MSU-induced inflammation as evidenced by a decrease of the ankle edema and inflammatory cell infiltration and a significant downregulation of the protein level of NFκB, TNFα, IL-1β, IL6, and IL18 as well as NLRP3 gene expression. Additionally, there was a markedly increased PPARγ gene expression (p < 0.001) compared with the MSU group (p < 0.001) and alleviated oxidative stress via significant upregulating of Nrf2/HO-1. Moreover, the pretreatment attenuated apoptosis by significantly decreasing cytochrome c, Bax, Caspase-3, and by increasing Bcl-2 protein. In conclusion, Stevia extract exhibited strong anti-inflammatory, antioxidant, and antiapoptotic effects against MSU-induced gouty arthritis similar to the standard anti-inflammatory colchicine drugs. [ABSTRACT FROM AUTHOR]

Chemo fog is one of the most serious health concerns encountered by cancer survivors receiving doxorubicin (DOX)-based chemotherapy. Oxidative stress, neuroinflammation, apoptosis and impairment of synaptic plasticity are regarded as the key factors implicated in DOX-induced cognitive impairment. This research aimed to assess the possible neuroprotective effect of cerium oxide nanoparticles (CeNPs) against DOX-induced neurotoxicity. Forty-eight rats were divided into four groups (12 rats/group): control group, CeNPs group (received oral CeNPs solution (35 mg/kg) daily for 4 weeks), and DOX group (were administered DOX intraperitoneally (2 mg/kg, once/week for 4 weeks)) and DOX+ CeNPs group. The findings revealed that CeNPs mitigated behavioral alterations in DOX-induced cognitive deficit. Additionally, CeNPs alleviated the histopathological abnormalities in hippocampus and ameliorated DOX-induced neuroinflammation by downregulating the expression of NF-κB, TNF-α, IL-1β and IL6. In addition, CeNPs antagonized the apoptosis through reducing the protein expression of cytochrome c and caspase 3. In addition, it stimulated the antioxidant defense, as indicated by upregulating the expression of the Nrf2, HO-1 and PGC-1α genes. CeNPs improved synaptic plasticity via acting on the BDNF. These actions were related through the modification of SIRT-1 expression. Based on the aforementioned results, CeNPs antagonized the doxorubicin-induced neurodegeneration by its antioxidant, anti-inflammatory and antiapoptotic effects, alongside its SIRT-1 mediated mechanisms. [ABSTRACT FROM AUTHOR]

Cisplatin, a platinum chemotherapeutic agent, is used in a diversity of malignancies; nevertheless, the excessive nephrotoxicity following cisplatin treatment is the dose-limiting devastating reaction. This study was designed to explore the possible nephroprotective impact of wogonin, a forceful anti-oxidant, anti-inflammatory, and anti-tumor agent, in a rat model of cisplatin-induced renal injury. The potential nephroprotective mechanisms were additionally investigated. Wogonin was given at a dose of 40 mg/kg. Acute nephrotoxicity was indicated by a significant rise in BUN, and serum creatinine levels in cisplatin-injected rats. Also, cisplatin enhanced the lipid peroxidation, diminished GSH, catalase, and PPAR-γ levels. Additionally, cisplatin-injected rats showed a significant rise in tissue levels of IL-1β, TNF-α, NF-kB, and caspase-3 enzymatic activity. Notably, the pre-treatment with wogonin ameliorated the nephrotoxicity indices, oxidative stress, inflammation, and apoptosis induced by cisplatin. Also, wogonin up-regulated PPAR-γ expression. The involvement of Wnt/β-catenin pathway was debatable; however, our findings showed that it was significantly induced by cisplatin. Wogonin pre-treatment markedly attenuated Wnt/β-catenin pathway. Collectively, these findings imply that wogonin is a promising nephroprotective agent that improves the therapeutic index of cisplatin via reducing oxidative stress, inflammation as well as inducing PPAR-γ. Also, Wnt/β-catenin pathway is partially involved in the pathogenesis of cisplatin nephrotoxicity. • Pre-treatment with wogonin showed a promising nephroprotection against cisplatin. • Wogonin attenuated cisplatin-induced oxidative stress and inflammation. • Wogonin reduced apoptosis and enhanced PPAR-γ expression in kidney tissues. • Wogonin attenuated Wnt/beta-catenin pathway expression. • Wogonin enhances the therapeutic index of cisplatin. [ABSTRACT FROM AUTHOR]

One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1b), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R. [ABSTRACT FROM AUTHOR]