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.

Bioremediation treatment improves water quality for Nile tilapia (Oreochromis niloticus) under crude oil pollution.

Despite favorable publicity of bioremediation as an affordable technology for cleanup of crude oil, public concerns on ecological safety in the presence of residual oil remain a global challenge. In this study, effects of crude oil exposure at sublethal concentration (0.25% v/v) and bioremediation treatment were investigated on histology and biochemical parameters of organs (gills, liver, kidney, and brain) of juvenile Nile tilapia (Oreochromis niloticus). Ten percent (10%) of mixed bacterial culture was used for bioaugmentation treatment. Ninety juvenile fish were used for study, and experiments were carried out in triplicates for three different groups. Malondialdehyde (MDA), an index of lipid peroxidation, was assayed as biomarker for oxidative stress. Activities of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), level of non-enzymatic antioxidant (reduced glutathione (GSH)), and activity of brain acetylcholinesterase (AChE) were assayed in selected fish organs as markers for environmental stressor. Histological examination of fish organs was done for all groups. Results of treated groups were compared with those of the control. Levels of MDA significantly increased with significant inhibition of antioxidant enzyme activities in the polluted group. Activities of SOD, CAT, and AChE and levels of GSH in fish organs in the bioaugmentation group were similar to results obtained in the control. Remarkably, the bioaugmentation group showed minimal or no lesions which suggested the efficacy of bioremediation technique in alleviating crude oil toxicity and preserving normal physiology of fish. This study provides deeper insights into the ecosafety of bioremediation treatment and can be extrapolated to other species of fish.

The ethanol leaf extract of Andrographis paniculata blunts acute renal failure in cisplatin-induced injury in rats through inhibition of Kim-1 and upregulation of Nrf2 pathway.

Background Cisplatin (CP) is a novel drug of choice in the treatment of cancer but its major limitation is nephrotoxicity, which is dose limiting. Andrographis paniculata (AP) is a common Indian dietary component. It is well known for its medicinal properties. This present study investigated the nephroprotective effect of ethanol leaf extract of Andrographis paniculata (EEAP) on CP-induced nephrotoxicity. Methods CP was used to induce nephrotoxicity in male Wistar rats to study the effect of EEAP on renal damages using hematological parameters, biochemical parameters, histology, and immunohistochemistry studies. Results The effects of EEAP were determined by CP-induced changes in different kidney tissue on antioxidant enzymes, markers of oxidative stress, serum creatinine, and urine parameters. Administration of EEAP (200 mL/kg and 400 mg/kg orally), prior to and following a single dose CP treatment (10 mg/kg i.p), significantly mitigated the CP-induced decrease in antioxidant enzymes, and increase in markers of oxidative stress, serum creatinine, and urinary protein. On histopathological examination of the kidney tissue, there was severe glomerular degeneration and infiltration of inflammatory cells in CP only treated rats, mild glomerular degeneration, and infiltration of inflammatory cells in EEAP pre-treated rats. Furthermore, EEAP activated Nrf2 and mitigated Kim-1 pathways in CP-induced nephrotoxicity. Conclusions The results showed the protective effect of EEAP against CP-induced nephrotoxicity.

Polyphenol-Rich Fraction of Parquetina nigrescens Mitigates Dichlorvos-Induced Cardiorenal Dysfunction Through Reduction in Cardiac Nitrotyrosine and Renal p38 Expressions in Wistar Rats.

Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined. Dichlorvos exposure caused a significant decrease in L-glutathione (reduced glutathione) and other antioxidant enzymes with increases in malondialdehyde, myeloperoxidase, advanced oxidation protein products, and protein carbonyl levels. It also brought about alterations in microanatomy of the heart and kidneys accompanied by increases in serum creatinine and urea levels. Exposure to dichlorvos induced prolonged QRS interval and shortened QT durations in rats. Immunohistochemistry revealed lower expressions of cardiac nitrotyrosine and renal p38 (mitogen-activated protein kinase; MAPK) in rats treated with prf of P. nigrescens. Combining all, prf of P. nigrescens demonstrated antioxidant as well as protective properties in the heart and kidneys of rats exposed to dichlorvos. It ameliorated dichlorvos-induced cardio- and nephrotoxicity giving credence to its use in ethnomedicine.

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.