Neuroprotective Assessment of Betaine against Copper Oxide Nanoparticle-Induced Neurotoxicity in the Brains of Albino Rats: A Histopathological, Neurochemical, and Molecular Investigation.

Copper oxide nanoparticles (CuO-NPs) are commonly used metal oxides. Betaine possesses antioxidant and neuroprotective activities. The current study aimed to investigate the neurotoxic effect of CuO-NPs on rats and the capability of betaine to mitigate neurotoxicity. Forty rats; 4 groups: group I a control, group II intraperitoneally CuO-NPs (0.5 mg/kg/day), group III orally betaine (250 mg/kg/day) and CuO-NPs, group IV orally betaine for 28 days. Rats were subjected to neurobehavioral assessments. Brain samples were processed for biochemical, molecular, histopathological, and immunohistochemical analyses. Behavioral performance of betaine demonstrated increasing locomotion and cognitive abilities. Group II exhibited significantly elevated malondialdehyde (MDA), overexpression of interleukin-1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Significant decrease in glutathione (GSH), and downregulation of acetylcholine esterase (AChE), nuclear factor erythroid 2-like protein 2 (Nrf-2), and superoxide dismutase (SOD). Histopathological alterations; neuronal degeneration, pericellular spaces, and neuropillar vacuolation. Immunohistochemically, an intense immunoreactivity is observed against IL-1ß and glial fibrillary acidic protein (GFAP). Betaine partially neuroprotected against CuO-NPs associated alterations. A significant decrease at MDA, downregulation of IL-1ß, and TNF-α, a significant increase at GSH, and upregulation of AChE, Nrf-2, and SOD. Histopathological alterations partially ameliorated. Immunohistochemical intensity of IL-1ß and GFAP reduced. It is concluded that betaine neuroprotected against most of CuO-NP neurotoxic effects through antioxidant and cell redox system stimulating efficacy.

Ameliorative effect of N-acetylcysteine on the testicular tissue of adult male albino rats after glyphosate-based herbicide exposure.

Glyphosate (GLP) is a broad-spectrum herbicide that is frequently used in crop production, but its residues remain in foodstuffs. This, in turn, has led to potential adverse effects on both human and animal health. Recent studies emphasized that GLP induces teratogenic effects and reproductive disorders, but its mechanism of toxicity is highly debated. N-acetylcysteine (NAC) is well known for its potent antioxidant capacity in addition to anti-inflammatory and cytoprotective properties. Therefore, our study aimed to investigate the reproductive toxicity of GLP in mature rats and evaluate the possible ameliorative effect of NAC against this toxicity. To this end, 30 adult male rats were assigned into three groups (10 rats per group) as follows: Group I, negative control; group II, GLP-exposed; 375 mg/kg GLP, orally; group III, NAC-cotreated, 160 mg/kg NAC 1 h before GLP, plus GLP, 375 mg/kg orally for 6 weeks. At the end of the experiment, the testicles were collected for semen analysis and biochemical, histopathological, and immunohistochemical studies. GLP-exposed rats exhibited disturbances in seminal parameters and a significant increase in malondialdehyde levels and expression of apoptotic markers. Several histopathological changes were observed, including strong immunoreactions for caspase-3 and proliferating cell nuclear antigen. Conversely, the administration of NAC before GLP was able to improve seminal parameters, attenuate the induced oxidative stress and apoptosis in addition to the regeneration of testicular damage. In conclusion, NAC can ameliorate the reproductive toxicity induced by GLP to an acceptable degree.

Ameliorative effect of N-acetylcysteine against glyphosate-induced hepatotoxicity in adult male albino rats: histopathological, biochemical, and molecular studies.

Glyphosate (GLP) is the most commonly used herbicide that presents many hazards to the environment and living organisms. The present study aimed to explore hepatotoxic properties of GLP on adult albino rats, and the ability of N-acetylcysteine (NAC) to ameliorate these toxic effects. Thirty mature male albino rats were distributed into 3 groups (10 rats/group): Group I (C) a negative control, Group II (GLP) orally administered Roundup 0.8503 ml/kg/day which contain GLP (375 mg/kg) (1/10 of LD50) by gavage needle, and Group III (NAC+ GLP) received NAC (160 mg/kg, 1h before Roundup) by gavage needle and Roundup (0.8503 ml/kg) orally for 6 weeks. Blood and liver samples were collected and processed for biochemical, histopathological, ultrastructural, and immunohistochemical investigations. Group II displayed a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels, as well as overexpression of apoptotic markers. The total antioxidant capacity "TAC" and mRNA expression of NRF2 were significantly decreased. Concerning the histopathological findings, there were various degenerative changes as the hepatocytes showed hydropic swelling with nuclear pyknosis. These alterations were confirmed ultrastructurally as most of the cytoplasmic organelles were lost and the mitochondria appeared to deteriorate. Immunohistochemical results showed intense immunoreactivity against proliferating cell nuclear antigen (PCNA) and caspase-3. NAC administration before GLP partially ameliorates these alterations. ALT, AST, and MDA levels as well as expression of apoptotic markers were significantly reduced. TAC and mRNA expression of NRF2 were significantly increased. Histopathological alterations were partially improved as the hepatocytes returned normal and ultrastructurally they showed nearly normal cytoplasmic organelles. Additionally, the intense expression of PCNA and caspase-3 was significantly reduced. We concluded that NAC can ameliorate most of the adverse effects of GLP exposure through its antioxidant property and free radicals scavenging capacity.