The protective role of L-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats.

Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. L-Carnitine (LC) is regarded as the "gatekeeper" in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.

The Synergistic Influence of Polyflavonoids from Citrus aurantifolia on Diabetes Treatment and Their Modulation of the PI3K/AKT/FOXO1 Signaling Pathways: Molecular Docking Analyses and In Vivo Investigations.

This study was aimed at probing the modulatory influence of polyflavonoids extracted from Citrus aurantifolia, lemon peel extract (LPE-polyflavonoids), on attenuating diabetes mellitus (DM) and its complications. HPLC investigations of the LPE exhibited the incidence of five flavonoids, including diosmin, biochanin A, hesperidin, quercetin, and hesperetin. The in silico impact on ligand-phosphatidylinositol 3-kinase (PI3K) interaction was investigated in terms of polyflavonoid class to explore the non-covalent intakes and binding affinity to the known protein active site. The drug likeness properties and pharmacokinetic parameters of the LPE-polyflavonoids were investigated to assess their bioavailability in relation to Myricetin as a control. Remarkably, the molecular docking studies demonstrated a prominent affinity score of all these agents together with PI3K, implying the potency of the extract to orchestrate PI3K, which is the predominant signal for lessening the level of blood glucose. To verify these findings, in vivo studies were conducted, utilizing diabetic male albino rats treated with LPE-polyflavonoids and other groups treated with hesperidin and diosmin as single flavonoids. Our findings demonstrated that the LPE-polyflavonoids significantly ameliorated the levels of glucose, insulin, glycogen, liver function, carbohydrate metabolizing enzymes, G6Pd, and AGEs compared to the diabetic rats and those exposed to hesperidin and diosmin. Furthermore, the LPE-polyflavonoids regulated the TBARS, GSH, CAT, TNF-α, IL-1ß, IL-6, and AFP levels in the pancreatic and hepatic tissues, suggesting their antioxidant and anti-inflammatory properties. In addition, the pancreatic and hepatic GLUT4 and GLUT2 were noticeably increased in addition to the pancreatic p-AKT in the rats administered with the LPE-polyflavonoids compared to the other diabetic rats. Remarkably, the administration of LPE-polyflavonoids upregulated the expression of the pancreatic and hepatic PI3K, AMPK, and FOXO1 genes, emphasizing the efficiency of the LPE in orchestrating all the signaling pathways necessitated to reduce the diabetes mellitus. Notably, the histopathological examinations of the pancreatic and hepatic tissues corroborated the biochemical results. Altogether, our findings accentuated the potential therapeutic role of LPE-polyflavonoids in controlling diabetes mellitus.

Efficiency of Biobran/MGN-3, an Arabinoxylan Rice Bran, in Attenuating Diabetes-Induced Cognitive Impairment of the Hippocampus via Oxidative Stress and IR/Akt/NF-κB in Rats.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease accompanied by cognitive impairment, hippocampal malfunctioning, and inflammation. Biobran/MGN-3, an arabinoxylan rice bran, has been shown to have an antidiabetic effect in streptozotocin-induced diabetic rats. The present study investigates Biobran's effect against diabetes-induced cognitive impairment and synaptotoxicity in the hippocampus via oxidative stress and the IR/A/NF-κB signaling pathway in rats. Diabetes was induced via i.p. injection of streptozotocin (STZ) (40 mg/kg BW); STZ-treated rats were then administered Biobran (100 mg/kg BW) for 4 wks. Biobran supplementation improved motor coordination and muscular strength, as assessed by Kondziella's inverted screen test. Biobran also improved concentration levels of glutathione (GSH), antioxidant enzymes, acetylcholine (ACh), dopamine, serotonin, insulin receptor (IR), and alpha serine-threonine protein kinase (Akt); it protected against elevated levels of glucose, total cholesterol, triglycerides, oxidative stress markers, TBARS, NO, AChE, and MAO; and it significantly decreased inflammatory cytokines levels of IL-1ß, NF-κB, TNF-α, and amyloid ß1-42. Moreover, Biobran ameliorated hippocampal histological alterations. Immunohistochemical observations showed that Biobran reduced overexpression of hippocampal synaptophysin and Ki67 relative to untreated diabetic rats. Biobran may ameliorate hippocampal alterations in diabetic rats via its antidiabetic, antiproliferative, anti-inflammatory, antiapoptotic, and antioxidant effects.

Antidiabetic efficacy of Trifolium alexandrinum extracts hesperetin and quercetin in ameliorating carbohydrate metabolism and activating IR and AMPK signaling in the pancreatic tissues of diabetic rats.

Diabetes is a metabolic disease that is mainly characterized by hyperglycemia. The present work investigated the efficacy of the flavanones hesperetin (HES) and quercetin (Q) extracted from Trifolium alexandrinum (TA) to treat type 2 diabetic rats. Wistar albino rats were supplemented with a high fat diet (HFD) for 2 weeks and then administered streptozotocin to induce diabetes. Diabetic rats were orally treated with Q, HES, and TA extract at concentrations of 40, 50, and 200 mg/kg BW, respectively, for 4 weeks. Various biochemical, molecular, and histological analysis were performed to evaluate the antidiabetic effects of these treatments. Q, HES, and TA extract treatments all significantly improved diabetic rats' levels of serum glucose, insulin, glucagon, liver function enzymes, hepatic glycogen, α-amylase, lipase enzymes, lipid profiles, oxidative stress indicators, and antioxidant enzymes as compared with control diabetic untreated rats. In addition, supplementation with Q, HES, and TA extract attenuated the activities of glucose-6-phosphate; fructose-1,6-bisphospahate; 6-phosphogluconate dehydrogenase; glucose-6-phosphate dehydrogenase; glucokinase; and hexokinase in pancreatic tissue, and they improved the levels of glucose transporter 2 and glucose transporter 4. Furthermore, these treatments modulated the expressions levels of insulin receptor (IR), phosphoinositide 3-kinase (PI3K), AMP-activated protein kinase (AMPK), caspase-3, and interleukin-1ß (IL-1ß). Enhancement of the histological alterations in pancreatic tissues provided further evidence of the ability of Q, HES, and TA extract to exert antidiabetic effects. Q, HES, and TA extract remedied insulin resistance by altering the IR/PI3K and AMPK signaling pathways, and they attenuated type 2 diabetes by improving the antioxidant defense system.

Neurotoxicity and neuroinflammatory effects of bisphenol A in male rats: the neuroprotective role of grape seed proanthocyanidins.

Exposure to bisphenol A (BPA) contributes to neurological disorders, but the underlying mechanisms are still not completely understood. We studied the neurotoxic effect of BPA and how it promotes inflammation and alteration in the neurotransmission synthesis, release, and transmission. This study was also designed to investigate the neuroprotective effect of grape seed proanthocyanidins (GSPE) against BPA-induced neurotoxicity in rats. Rats were equally divided into 4 groups with 7 rats in each: control group, BPA group, GSPE + BPA group, and GSPE group. Rats were orally treated with their respective doses (50 mg BPA/kg BW and/or 200 mg GSPE/kg BW) daily for 70 days. BPA elicits significant elevation in malondialdehyde (MDA) and nitric oxide (NO) associated with a significant reduction in glutathione (GSH), total thiols, glutathione peroxidase (GPx), superoxide dismutase (SOD), and glutathione-S-transferase (GST). BPA exposure results in increased dopamine and serotonin levels, elevation in acetylcholinesterase (AChE) activity, and reduction in Na/K-ATPase and total ATPase activities in the brain. Also, BPA induces upregulation in the gene expression of the inflammatory markers, tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2), and in the tumor suppressor and pro-oxidant p53 protein. The pretreatment with GSPE attenuates or ameliorate all the oxidative and neurotoxic parameters induced by BPA. Our results suggest that GSPE has a promising role in modulating BPA-induced neuroinflammation and neurotoxicity and its antioxidant and free radical scavenging activities may in part be responsible for such effects.

Hepatoprotective effect of Spirulina platensis against carbon tetrachloride-induced liver injury in male rats.

OBJECTIVES: Spirulina platensis (SP) is an edible Cyanobacterium with ethnomedicinal significance. This study aims at evaluating the beneficial effect of SP against carbon tetrachloride (CCl4)-induced liver toxicity in male rats. METHODS: Rats received intraperitoneal injections of CCl4 (2 ml/kg body weight [b.w.] per every other day) for 40 days, alone or in combination with oral treatments of SP (400 mg/kg b.w. per day). KEY FINDINGS: SP attenuated haematological disturbances, serum liver markers, hepatic necrosis and inflammation, and dyslipidemia in CCl4-intoxicated rats. SP also reduced CCl4-induced oxidative stress by increasing the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase and glutathione content, and inhibiting lipid peroxidation products and nitric oxide levels in the rat liver. Further investigations revealed that SP counteracted CCl4-induced increased hepatic levels of Ki-67 (a parameter of cell proliferation), interleukin-6, and tumour necrosis factor-alpha and cyclooxygenase-2 messenger RNA expression. Noticeably, the supplementation of SP restored the decrease of proapoptotic p53 protein levels in the liver of rats treated with CCl4. CONCLUSIONS: SP prevented liver damage in CCl4-treated rats via augmentation of antioxidant defense mechanisms and inhibition of inflammatory cytokines/mediators and antiproliferative effects.

Oral Supplements of Ginkgo biloba Extract Alleviate Neuroinflammation, Oxidative Impairments and Neurotoxicity in Rotenone-Induced Parkinsonian Rats.

BACKGROUND: Ginkgo biloba extract (GbE) is known to contain several bioactive compounds and exhibits free radical scavenging activity. Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. OBJECTIVE: The current study aimed to investigate the neuroprotective effect of GbE in a rat model of PD induced by rotenone (ROT; a neurotoxin). METHODS: Twenty-four male albino rats were randomly divided into four groups of six rats each: normal control, GbE treated, toxin control (ROT treated) and GbE+ROT group. RESULTS: Oral administration of ROT (2.5 mg/kg b.w.) for 50 days caused an increased generation of lipid peroxidation products and significant depletion of reduced glutathione, total thiol content and activities of enzymatic antioxidants, i.e., superoxide dismutase and glutathione peroxidase in the brains of treated rats. Furthermore, ROT caused an elevation in acetylcholinesterase, interleukin-1ß, interleukin- 6 and tumor necrosis factor-α and a significant reduction in dopamine in the stratum and substantia nigra. Immunohistochemical results illustrated that ROT treatment reduced the expression of tyrosine hydroxylase (TH). GbE treatment (150 mg/kg b.w./day) significantly reduced the elevated oxidative stress markers and proinflammatory cytokines and restored the reduced antioxidant enzyme activities, DA level and TH expression. These results were confirmed by histological observations that clearly indicated a neuroprotective effect of GbE against ROT-induced PD. CONCLUSION: GbE mitigated ROT-induced PD via the inhibition of free-radical production, scavenging of ROS, and antioxidant enhancement.

Bisphenol A-induced oxidative damage in the hepatic and cardiac tissues of rats: The modulatory role of sesame lignans.

Bisphenol A (BPA) is an environmental pollutant that is widely produced throughout the world. It is primarily used in the manufacture of polycarbonate plastics, epoxy resins, paints and dental materials. BPA has been reported to promote hepatotoxicity and cardiotoxicity. The antioxidant activity of sesame lignans is well established. The current study assessed the protective efficiency of sesame lignans against BPA-induced hepatotoxicity and cardiotoxicity. Rats were divided into 4 groups: A control group, a BPA-treated group, a sesame lignans-treated group and a sesame lignans and BPA-treated group. Rats were orally administered their respective doses daily [30 mg/kg body weight (BW) BPA and/or 20 mg/kg BW sesame lignans] for 6 weeks. Liver function tests were performed using serum of all groups. Lipid profile and antioxidant status were also measured in liver tissue of the studied groups. The results were confirmed by histopathological examination of liver and heart tissues. The oral administration of BPA was revealed to elicit significant decreases in the activities of hepatic glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione. It also significantly increased levels of malondialdehyde. Furthermore, BPA-treatment resulted in lipid accumulation, elevated activities of alanine aminotransferase, creatine kinase MB and lactate dehydrogenase, and histological changes of liver and heart tissues. However, the co-administration of sesame lignans and BPA attenuated hepatotoxicity, cardiotoxicity and BPA-induced histological changes. The results of the current study indicated that sesame lignans may be helpful in the development of novel natural drugs to treat hepatic and cardiovascular disorders.

Neuro- and nephroprotective effect of grape seed proanthocyanidin extract against carboplatin and thalidomide through modulation of inflammation, tumor suppressor protein p53, neurotransmitters, oxidative stress and histology.

The combination of thalidomide and carboplatin is one of the most potent chemotherapeutic strategies for the treatment of cancer. However, limited studies have been conducted on the neurotoxicity and nephrotoxicity of both chemotherapeutic agents. The aim of our study was to assess the toxicity of thalidomide and carboplatin combination on brain and kidney and investigate the protective effect of grape seed proanthocyanidin extract (GSPE). Thalidomide and carboplatin induced up-regulation of the expression of p53, tumor necrosis factor-α and interleukin-6 in brain and kidney. Acetylcholinesterase, dopamine and serotonin were decreased and norepinephrine was increased. Thiobarbituric acid reactive substances, nitric oxide, lipid profile, bilirubin and creatinine were elevated, while antioxidants enzymes (GST, GPX, CAT and SOD), total antioxidant capacity and the levels of glutathione were decreased. A microscopic examination showed shrinkage of capillaries, degeneration with pyknotic nuclei, loss of normal structure and neuronal degeneration. GSPE co-treatment with thalidomide and carboplatin reduced their brain and renal damage, oxidative stress, diminished cytokines, p53, neurotransmitters and biochemical parameters, and inhibited brain and renal cell apoptosis. It can be concluded that, the protective effects of GSPE against thalidomide and carboplatin induced-brain and renal damage was associated with the minimization of oxidative stress.

Neuroprotection of Grape Seed Extract and Pyridoxine against Triton-Induced Neurotoxicity.

Triton WR-1339 administration causes neurotoxicity. Natural products and herbal extracts can attenuate cerebral injury. In the present study, we investigated the neuroprotective role of grape seed extract and/or vitamin B6 against triton-induced neurotoxicity. Thirty-five adult male albino rats of the Sprague-Dawley strain, weighing 140-145 g, were divided into five groups: control, triton, grape seed extract + triton, grape seed extract + triton + vitamin B6, and vitamin B6 + triton. The hematological and biochemical analyses were carried out. Alteration in iNOS mRNA gene expression was determined using reverse-transcriptase PCR analysis. In addition, qualitative DNA fragmentation was examined using agarose gel electrophoresis. Triton-treatment caused significant disturbances in the hematological parameters, the neurological functions, and the antioxidant profile. Also, triton significantly increased the iNOS mRNA expression and DNA damage. Our results showed that grape seed extract and/or vitamin B6 could attenuate all the examined parameters. These natural substances could exhibit protective effects against triton-induced neurological damage because of their antioxidative and antiapoptotic capacities.

Prophylactic neuroprotective efficiency of co-administration of Ginkgo biloba and Trifolium pretense against sodium arsenite-induced neurotoxicity and dementia in different regions of brain and spinal cord of rats.

The present study was carried out to evaluate the potential protective role of co-administration of Ginkgo biloba, Trifolium pretenseagainst sodium arsenite-induced neurotoxicity in different parts of brain (Cerebral cortex, Hippocampus, striatum and Hind brain) and in the spinal cord of rats. Sodium arsenite caused impairment in the acquisition and learning in all the behavioral tasks and caused significant increase in tumor necrosis factor-α,thiobarbituric acid-reactive substances andlipid profile, while caused significant decrease in glutathione, total thiol content, total antioxidant capacity, acetylcholinesterase, monoamine oxidase and ATPases activities. These results were confirmed by histopathological, fluorescence and scanning electron microscopy examination of different regions of brain. From these results sodium arsenite-induced neurodegenerative disorder in different regions of brain and spinal cord and this could be mediated through modifying the intracellular brain ions homeostasis, cholinergic dysfunction and oxidative damage. The presence of Ginkgo biloba and/orTrifolium pretense with sodium arsenite minimized its neurological damages. It was pronounced that using Ginkgo biloba and Trifolium pretense in combination was more effective as protective agents compared to use eachone of them alone.

Protective role of omega-3 polyunsaturated fatty acid against lead acetate-induced toxicity in liver and kidney of female rats.

The present study was conducted to investigate the protective role of Omega-3 polyunsaturated fatty acids against lead acetate-induced toxicity in liver and kidney of female rats. Animals were divided into four equal groups; group 1 served as control while groups 2 and 3 were treated orally with Omega-3 fatty acids at doses of 125 and 260 mg/kg body weight, respectively, for 10 days. These groups were also injected with lead acetate (25 mg/kg body weight) during the last 5 days. Group 4 was treated only with lead acetate for 5 days and served as positive control group. Lead acetate increased oxidative stress through an elevation in MDA associated with depletion in antioxidant enzymes activities in the tissues. Moreover, the elevation of serum enzymes activities (ALT, AST, ALP, and LDH) and the levels of urea and creatinine were estimated but total proteins were decreased. Also, lead acetate-treatment induced hyperlipidemia via increasing of lipid profiles associated with decline in HDL-c level. Significant changes of Hb, PCV, RBCs, PLT, and WBCs in group 4 were recorded. The biochemical alterations of lead acetate were confirmed by histopathological changes and DNA damage. The administration of Omega-3 provided significant protection against lead acetate toxicity.

Cypermethrin induced damage in genomic DNA and histopathological changes in brain and haematotoxicity in rats: the protective effect of sesame oil.

The protective effect of sesame oil against cypermethrin-induced brain toxicity was studied. Female rats were orally treated with cypermethrin, sesame oil and their combination for 30 consecutive days. The results showed that cypermethrin increased thiobarbituric acid-reactive substances (TBARS), and decreased glutathione (GSH) and the activities of the antioxidant enzymes. Brain injury was confirmed by histopathological changes and DNA damage. Also, the reduction in the activities of acetylcholinesterase and monoamine oxidase (AChE & MAO), total protein, albumin and body weight, and the induction in triacylglycerol and cholesterol have been observed due to cypermethrin toxicity. Animals treated with sesame oil and cypermethrin together showed that brain TBARS and plasma triacylglycerol and cholesterol returned to the control level which indicating a protective effect of sesame oil. Also, sesame oil was able to attenuate the decrease in total protein, albumin, triacylglycerol and cholesterol, GSH, AChE and antioxidant enzymes induced by cypermethrin. In addition, sesame oil protected the brain histological changes and fragmentation of genomic DNA in animals treated with cypermethrin. The present results showed a protective effect of sesame oil against the cypermethrin induced brain toxicity and this could be associated mainly with the attenuation of the oxidative stress and the preservation in antioxidant enzymes.

Deleterious effects of cypermethrin on rat liver and kidney: protective role of sesame oil.

The involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides. Our study was designed to investigate the induction of oxidative stress by cypermethrin; a Type II pyrethroid in rat liver and kidney. In addition, the protective role of sesame oil against the toxicity of cypermethrin was investigated. Animals were divided into four equal groups; the first group used as control while groups 2, 3 and 4 were treated with sesame oil (5 mL/kg b.w), cypermethrin (12 mg/kg b.w) and the combination of both sesame oil (5 mL/kg b.w) plus cypermethrin (12 mg/kg b.w), respectively. Rats were daily administered with their respective doses for 30 days by gavage. Repeated oral administration of cypermethrin was found to reduce the level of glutathione (GSH) and the activities of the antioxidant enzymes. While, the level of TBARS was elevated indicating the presence of oxidative stress. The activities of LDH, AST and ALT were decreased in the liver extract while increased in the plasma of the cypermethrin-treated group. Also, the levels of urea and creatinine were significantly increased after treatment with cypermethrin. Liver and kidney injury was confirmed by the histological changes. In conclusion, the administration of sesame oil provided significant protection against cypermethrin-induced oxidative stress, biochemical changes, histopathological damage and genomic DNA fragmentation.

Protective role of flax lignans against lead acetate induced oxidative damage and hyperlipidemia in rats.

The results showed that the lead concentration was higher than Cr, Ni and Cd in roadside soil samples. Also, the present study was conducted to investigate the protective role of flax lignans against the effects of lead acetate on oxidative stress, antioxidant enzymes and lipid profile. Animals were divided into three groups; the first group was used as control. While, groups 2, and 3 were orally treated with 200 mg/L lead acetate in drinking water and the combination of lead acetate (200 mg/L) plus flax lignans (30 mg/100 g BW), respectively. Rats were administered their respective doses daily for 3 weeks. Results showed that lead acetate increased TBARS, and decreased the activities of GST, SOD, GR and CAT, and the contents of glutathione in liver extracts, compared to control. The present data indicated that total lipids, cholesterol, triglycerides and LDL-c were significantly increased by lead acetate treatment, while HDL-c levels were decreased in the serum and liver extracts. Animals treated with flax lignans in combination with lead acetate alleviated its toxic effects in the tested parameters. Also, the morph metric analysis of the dorsal aorta revealed that, the histological alterations induced after lead acetate treatments were markedly reduced.