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.

Effect of the methanol extract of the red cultivar Allium cepa L. on the serum biochemistry and electrolytes of rats following sub-chronic oral administration.

Background In traditional medicine, Allium cepa Linnaeus is used for the treatment of several disease conditions. Whilst reports abound on the effects of several cultivars of A. cepa L on biochemical parameters, similar information on the red cultivar is scarce. This study examines the effects of the methanol extract of the red cultivar A. cepa L on some serum biochemical parameters in experimental Wistar rats. Materials and methods Fifty-five Wistar rats were divided into three groups (A, B and C), which include 25, 25 and 5 rats, respectively. The rats in Groups A and B were sub-divided into 5 groups of 5 rats. Each rat was administered a certain dose of methanol extract of the red cultivar A. cepa L for 14 days (Group A) or 28 days (Group B). Group C rats served as the control and were administered with distilled water (10 mL/kg). Results A. cepa L administration resulted in dyslipidaemia, hyponatremia, hypokalaemia and hyperchloraemia; a significant (p < 0.05) decrease in hepatic enzymes and a significant (p < 0.05) increase in serum bicarbonate, bilirubin and its fractions. Conclusions These biochemical results indicate that the excessive and prolonged medicinal consumption of A. cepa L products beyond 7 days may induce moderate hepatic injury and mild renal dysfunction and may complicate disease conditions, such as hypertension and diabetes. Thus, in order to minimize its toxic effects, it is recommended that A. cepa L products should not be used for more than seven consecutive days or beyond a dosage of 90 mg/kg.

Chronic inhalation of 2, 2-dichlorovinyl dimethyl phosphate (DDVP) induces organ pathology in the adult albino rats

The acute toxic effects of the acetyl cholinesterase-inhibiting pesticide, DDVP, following oral and dermal exposure are well recorded in literature. The ability of DDVP to easily vaporize makes the aero-nasal route a possible means of exposure, albeit chronically. This study aimed to describe the pathology, if any, of the heart, kidney and liver following chronic exposure to various concentrations of DDVP via inhalation.Sixty male Wistar rats were divided into 6 groups (A-F) of 10 rats each. Rats in Group A were exposed to distilled water only, while rats in groups B, C, D, E and F were exposed to 20, 40, 60, 80 and 100% v/v concentrated fumes of DDVP respectively. Duration of inhalational exposure was for 90 days. The heart, liver and kidney of the rats in the groups were extracted for routine histopathology. Organ pathologies were semi-quantitatively scored and analyzed across and between the 6 groups.Generally, lesions were of progressive severity with increasing concentrations of DDVP. Across the organs, pathology was related to altered vascular and degenerative changes. Specifically, the heart, kidney and liver showed shredding of cardiomyocytes, sloughing of renal tubular epithelial cells with dilated tubular lumina, and hepatocellular degeneration and necrosis respectively. Inflammatory changes were limited to the livers of rats exposed to 80 and 100% v/v DDVP.It was concluded that DDVP induced altered vascular and degenerative changes following chronic exposure via inhalation. Safer alternatives to aerosolized DDVP-containing insecticides are recommended for the control of arthropod vectors in enclosures

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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.

Anti-Hyperglycaemic Effect of Cleome Rutidosperma in Alloxan-Induced Diabetic Albino Rats.

The hypoglycaemic and antihyperglycaemic effects of methanol extract of leaves of Cleome rutidosperma (Cr) DC (Family: Capparidaceae) was investigated in Wistar rats. Fifty normoglycaemic male rats (120 g-200 g) were divided into groups A (hypoglycaemic study; n=20) and B (antihyperglycaemic study; n=30). Each experiment had one control group and three groups administered with Cr (100, 200 or 400 mg/kg) respectively. Group B had two additional groups of diabetic-untreated rats and glibenclamide-treated diabetic rats. Diabetes was induced in Group B rats (except control) fasted overnight for 12 h by intraperitoneal injection of Alloxan (100 mg/kg). Fasting blood glucose levels (FBGL) were determined and alloxan-treated rats with BGL >200 mg/dl 48 h post-induction were considered diabetic. Data obtained were analyzed using One-way ANOVA and Duncan Multiple Range Test (p<0.05). Cr-treated rats showed significant decline in BGL with noteworthy decline by day 3 post-treatment at the dose of 200 mg/kg (236.40±14.72 mg/dl) from 336.40±21.06 mg/dl. Cr at the dose of 200 mg/kg (72.20±6.18 mg/dl, 69.20±7.81 mg/dl, 137.80±7.15 mg/dl and 70.60±10.66 mg/dl) showed better glycemic control compared to glibenclamide (194.50±7.75 mg/dl, 253.75±7.20 mg/dl, 284.25±10.56 mg/dl and 156.00±10.80 mg/dl). Cr-treated rats also showed progressive weight gain through the course of the study. This study demonstrated Cr has antihyperglycemic effect with more rapid onset of action and better glycemic control compared to glibenclamide.

Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in Wistar rats.

Lead acetate (PbA) is one of the major environmental contaminants with grave toxicological consequences both in the developing and developed countries. The liver and erythrocyte antioxidant status and markers of oxidative were assessed. Exposure of rats to PbA led to significant decline (p < 0.05) in hepatic and erythrocyte glutathione peroxidase (GPx), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) content. Similarly, malondialdehyde (MDA) and H(2)O(2) concentrations were significantly (p < 0.05) elevated. Histopathology and immunohistology of liver of rats exposed to PbA showed focal areas of necrosis and COX-2 expression after 6 weeks of PbA withdrawal. Taken together, hepatic and erythrocytes antioxidant defence system failed to recover after withdrawal of the exposed PbA for the period of the study. In conclusion, experimental animals exposed to PbA did not recover from hepatotoxicity and disruption of erythrocyte antioxidant defence system via free radical generation and oxidative stress.

Hepatoprotective and in vivo antioxidant activities of ethanolic extract of whole fruit of Lagenaria breviflora.

BACKGROUND: This study was designed to investigate the hepatoprotective and in vivo antioxidant effects of the ethanol extract of whole fruit of Lagenaria breviflora (LB) in experimental animals. METHODS: Forty nine Wistar albino rats were divided into seven groups of seven. Group I served as the control group; rats in Group II were given i.p. carbon tetrachloride (CCL4) (1.5 mL/kg) alone; Groups III-VI received different concentrations of plant extract (100, 250 and 500 mg/kg) with CCL4 and Group VII received kolaviron (KV) at 200 mg/kg as a reference hepatoprotective agent. RESULTS: There was a significant (p<0.05) increase in malondialdehyde (MDA) and hydrogen peroxide (H202) generation in the serum of CCL4 treated rats (Group II) while the serum glutathione (GSH) level decreased significantly. Pretreatment with LB extract led to a significant (p<0.05) increase in serum GSH and a significant (p<0.05) reduction in MDA and H2O2generation. The activities of marker enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin, creatinine and blood urea nitrogen (BUN) increased (p<0.05) significantly in CCL4 treated rats (Group II). CONCLUSIONS: The present study suggested that treatment with LB extract enhances the recovery from CCL4 induced hepatic damage and oxidative stress via its antioxidant and hepatoprotective properties.

Anti-inflammatory and analgesic properties of the ethanolic extract of Cnidoscolus aconitifolius in rats and mice.

BACKGROUND: Ethanolic leaf extract of Cnidoscolus aconitifolius was evaluated for analgesic and anti-inflammatory activities. METHODS: The analgesic activity of the extract was assayed by the formalin-induced paw licking test, acetic acid-induced abdominal writhing and hot plate test, whereas its anti-inflammatory activity was determined by its effects on carrageenan-induced paw edema. RESULTS: The extract of C. aconitifolius prolonged the reaction time of mice to pain in a dose-dependent manner. The optimal analgesic effect of the extract was obtained when the extract was administered 90 min before pain stimulation in the hot plate test. The extract of C. aconitifolius (100 or 200 mg/kg b.w.) inhibited acetic acid-induced irritation of paws of rats comparably with that of indomethacin (10 mg/kg b.w.) and had significantly lower mean number of lickings of paws than the control rats (p<0.05). Carrageenan-induced edema was markedly inhibited (p<0.05) by the extracts (100 and 200 mg/kg b.w.) when compared with control rats. Inhibition of writhing movement in rats administered with the extract was lower (p<0.05) than rats administered with indomethacin but its effect was dose-dependent. CONCLUSIONS: Our investigations show that C. aconitifolius possesses significant anti-inflammatory and analgesic activities that should be explored.

Role of oxidative stress in reproductive toxicity induced by co-administration of chloramphenicol and multivitamin-haematinics complex in rats.

Concurrent administration of chloramphenicol (CAP) with multivitamin-haematinics complex (MHC) is a common practice to cushioning anticipated anaemic effect of CAP in most developing countries. This study investigated the mechanism involved in CAP-induced reproductive toxicity as well as the effects of its co-administration with MHC in male rats. CAP and MHC were administered orally at therapeutic doses of 28 mg/kg body-weight and 0.08 ml/kg body-weight, respectively, every 6 hr for 10 days. After exposure, while there was body-weight loss in CAP, MHC and CAP plus MHC-treated animals, there were no treatment-related changes in the absolute and relative weights of the testes in all treated groups. Alone, MHC treatment markedly decreased catalase (CAT), glutathione S-transferase (GST), and 5' nucleotidase (5' NTD) activities whereas it resulted in significant increase in superoxide dismutase (SOD) activity. Activities of SOD, CAT and GST as well as H(2)O(2) levels were not significantly affected in CAP and CAP plus MHC-treated rats whereas GSH level and 5' NTD activity were markedly decreased in CAP plus MHC-treated rats. Significant increase in testicular alkaline phosphatase activity, lipid peroxidation and sperm abnormalities were accompanied by reduction in epididymal sperm number, sperm motility and live-dead ratio in all treatment groups whereas aminotransferase activities were unaffected. Treatment-related degeneration of the testes was evident in all treated animals. In summary, while MHC-induced testicular toxicity via oxidative stress, CAP did not and their combination is implicated in reproductive dysfunction within the time course of our investigation.

Molecular targets of [6]-gingerol: Its potential roles in cancer chemoprevention.

A wide variety of phenolic compounds derived from spices possess potent antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic activities. [6]-gingerol (1-[4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) is the major pungent principle of ginger, with numerous pharmacological properties including antioxidant, anti-inflammation, and antitumor promoting properties. It could decrease inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha) expression through suppression of I-kappaB alpha (IkappaBalpha) phosphorylation, nuclear factor kappa B (NF-kappaB) nuclear translocation. Other antiproliferative mechanisms of [6]-gingerol include the release of Cytochrome c, Caspases activation, and increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction. Taken together, the chemopreventive potentials of [6]-gingerol present a promising future alternative to therapeutic agents that are expensive, toxic, and might even be carcinogenic.

Curcumin: from food spice to cancer prevention.

Curcumin [1, 7-bis (4-hydroxy-3-methoxyphenyl)-1, 6 heptadiene-3, 5-dione] is an orange-yellow component of turmeric (Curcuma longa), a spice often found in curry powder. It is known to have a variety of biologic and pharmacologic activities, including anti-inflammatory, anti-oxidant, and anticarcinogenic potential. It is a potent inhibitor of cytochrome P450 with capacity to simultaneously induce detoxifying enzymes such as glutathione S-transferase and as such may find application as a chemopreventive agent. Curcumin is a potent inhibitor of cyclooxygenase-2, lipooxygenase, ornithine decarboxylase (ODC), nuclear factor-kappaB, c-Jun N-terminal kinase and protein kinase C and has also been demonstrated to play a vital role against pathological conditions such as cancer, atherosclerosis, and neurodegenerative diseases.