Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression.

Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.

Moringa oleifera leaves ethanolic extract counteracts cortical neurodegeneration induced by aluminum chloride in rats.

Background: Aluminum, a well-recognized neurotoxin, is implicated in various neurodegenerative disorders. Moringa oleifera (M. oleifera), known as a miracle tree, is utilized as a functional food and nutritional supplement. This study investigates the potential preventive effects of M. oleifera extract on aluminum chloride (AlCl3)-induced cortical neurodegeneration in rats. Materials and methods: Therefore, 24 adult male Wistar rats were randomly divided into four distinct groups: negative control, M. oleifera extract (MOE), AlCl3, and AlCl3 + MOE. Treatments were administered orally for 28 consecutive days. Cognitive performance, brain oxidative/nitrosative stress, neuroinflammation, apoptotic-cell death, and associated histopathological alterations were assessed. Results: Our results showed that MOE improved spatial learning and memory, enhanced antioxidant superoxide dismutase enzyme activity, antagonized nitrosative stress, reduced inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), decreased caspase-3, increased Bcl-2, and facilitated repair of cortical and hippocampal structures. Conclusions: We concluded that MOE exhibits protective effects against cortical neurodegeneration, making it a promising supplement to counteract aluminum-induced neurotoxic effects.

In Vivo Wound-Healing Effect of Chemical and Green Synthesized Chitosan Nanoparticles Using Lawsonia inermis Ethanolic Extract.

Wounds can be a result of surgery, an accident, or other factors. There is still a challenge to find effective topical wound-healing agents. This study aims to investigate the wound-healing activity of chemical and green synthesized chitosan nanoparticles (Ch-NPs) using Lawsonia inermis leaves extract. The nanoparticles were morphologically and chemically characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and high-resolution transmission electron microscopy (HRTEM). Forty-five adult female albino rats were randomly divided into three groups. The cutaneous surgical wounds were topically treated with 0.9% normal saline (control group), green Ch-NPs (second group), and chemical Ch-NPs gels (third group), respectively. The clinical picture of wounds and histopathological changes were assessed on the 3rd, 7th, 14th, and 21st days post-treatment. X-ray diffraction analysis revealed great crystallinity and purity of nanoparticles. The studied nanoparticles increased the wound contraction percent (WC%), reduced healing time and wound surface area (WSA), and these results were backed up by histological findings that indicated improved epithelialization, dermal differentiation, collagen deposition, and angiogenesis in treated rats compared with control rats (p < 0.05). We concluded that the wound-healing effects of the studied nanoparticles are encouraging, and further studies for complete assessment are still needed.

Design, Synthesis, Biological Evaluation, and Molecular Dynamics Studies of Novel Lapatinib Derivatives.

Co-expression of the epidermal growth factor receptor (EGFR, also known as ErbB1) and human epidermal growth factor receptor 2 (HER2) has been identified as a diagnostic or prognostic sign in various tumors. Despite the fact that lapatinib (EGFR/HER2 dual inhibitor) has shown to be successful, many patients do not respond to it or develop resistance for a variety of reasons that are still unclear. As a result, new approaches and inhibitory small molecules are still needed for EGFR/HER2 inhibition. Herein, novel lapatinib derivatives possessing 4-anilinoquinazoline and imidazole scaffolds (6a-l) were developed and screened as EGFR/HER2 dual inhibitors. In vitro and in silico investigations revealed that compound 6j has a high affinity for the ATP-binding regions of EGFR and HER2. All of the designed candidates were predicted to not penetrate the BBB, raising the expectation for the absence of CNS side effects. At 10 µM, derivatives possessing 3-chloro-4-(pyridin-2-ylmethoxy)aniline moiety (6i-l) demonstrated outstanding ranges of percentage inhibition against EGFR (97.65-99.03%) and HER2 (87.16-96.73%). Compound 6j showed nanomolar IC50 values over both kinases (1.8 nM over EGFR and 87.8 nM over HER2). Over EGFR, compound 6j was found to be 50-fold more potent than staurosporine and 6-fold more potent than lapatinib. A kinase selectivity panel of compound 6j showed poor to weak inhibitory activity over CDK2/cyclin A, c-MET, FGFR1, KDR/VEGFR2, and P38a/MAPK14, respectively. Structure-activity relationship (SAR) that were obtained with different substitutions were justified. Additionally, molecular docking and molecular dynamics studies revealed insights into the binding mode of the target compounds. Thus, compound 6j was identified as a highly effective and dual EGFR/HER2 inhibitor worthy of further investigation.

Curcumin and cinnamon mitigates lead acetate-induced oxidative damage in the spleen of rats.

Lead toxicity is a common occupational and environmental health hazard that exerts many toxic effects on animals and humans, including immunotoxicity. Curcumin (CUR) and cinnamon (CIN) are common medicinal herbs with immunostimulatory and antioxidant properties. Therefore, this study investigated the protective effect of curcumin and cinnamon against lead acetate (LA)-induced splenotoxicity in rats via hemato-biochemical, immunological, oxidative stress marker, CYP-2E1 expression, histological, and immunohistological evaluations. Four groups of seven rats each were used: the control group received corn oil as a vehicle; the lead acetate group received (100 mg/kg), the CUR + LA group received curcumin (400 mg/kg) plus lead acetate, and the CIN + LA group received cinnamon (200 mg/kg) plus lead acetate orally for 1 month. LA exposure induced macrocytic hypochromic anemia, leukocytosis, neutrophilia, monocytosis, and lymphopenia. Additionally, significant elevations in serum iron, ferritin levels, and transferrin saturation percentage with significant decline of total and unsaturated iron binding capacities (TIBC and UIBC), transferrin, and immunoglobulin G and M levels were recorded. In addition, lead acetate significantly upregulated splenic CYP-2E1 expression, that was evident by significant depletion of reduced glutathione (GSH) activity and elevation of malondihyde (MDA), nitric oxide (NO), and protein carbonyl (PC) concentrations in the spleen. Histologically, hyperplasia of lymphoid follicles, hemosiderin deposition, and disturbance of CD3 and CD68 immuno-expressions were evident in the spleen from the lead acetate group. However, curcumin and cinnamon administration restored the hemato-biochemical, immunological, and oxidative stress parameters as well as histological and immunohistological pictures toward normalcy. In conclusion, curcumin and cinnamon can partially ameliorate LA-induced oxidative damage in the spleen, possibly through their antioxidant, immunomodulatory, and gene-regulating activities.