Clofibrate, a PPAR-α agonist, abrogates sodium fluoride-induced neuroinflammation, oxidative stress, and motor incoordination via modulation of GFAP/Iba-1/anti-calbindin signaling pathways.

Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator-activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and cerebellar Ca2+ -binding protein calbindin-D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders.

Ameliorative effect of gallic acid on doxorubicin-induced cardiac dysfunction in rats.

BACKGROUND: The use of doxorubicin (DOX) as an antineoplastic agent has been greatly limited because of the myriad of toxic sequelae associated with it. The aim of this study was to assess the protective effects of gallic acid (GA) on DOX-induced cardiac toxicity in rats. METHODS: Sixty male rats (Wistar strain) were used in this study. They were divided into six groups (A-F) each containing 10 animals. Group A was the control. Rats in Groups B, C, and D were treated with DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and 120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120 mg/kg GA, respectively, which were administered orally for 7 days. RESULTS: The exposure of rats to DOX led to a significant (p<0.05) decrease in the cardiac antioxidant defence system and elevation of creatine kinase myocardial band and lactate dehydrogenase. The electrocardiography results showed a significant decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the antioxidant defence system. CONCLUSIONS: The GA pretreatment significantly alleviated GA-associated ECG abnormalities, restored the antioxidant status and prevented cardiac damage.

Chemopreventive effect of methanolic extract of Azadirachta indica on experimental Trypanosoma brucei induced oxidative stress in dogs.

INTRODUCTION: The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. MATERIALS AND METHODS: Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed. RESULTS: Pre-treatment with methanolic extract of Azadirachta indica (MEAI) at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P < 0.05) decreased with pre-treatment with 50 mg/kg A. indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (P >0.05) difference compared to the values obtained in pre-treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05) decreased serum myeloperoxidase activity at 2 weeks post-infection with T. brucei. CONCLUSION: From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.