Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats.

Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and Drug Administration in 1977. However, TAM therapy is accompanied with hepatotoxicity - a source of worry to clinicians. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM hepatotoxicity. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced hepatotoxicity in female Wistar rats. Rats were subjected to oral pretreatment of Zn (100 mg/kg body weight (b.w.)/day) for 14 days against hepatic toxicity induced by single intraperitoneal administration of TAM (50 mg/kg b.w.) on day 13. TAM markedly elevated serum liver enzymes, whereas total protein and albumin considerably reduced. TAM caused prominent depletion of hepatic-reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity. Also, TAM significantly increased malondialdehyde (MDA) level. Further, it raised liver levels of tumor necrosis factor-α (TNF-α), interleukin-1ß, (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by the liver histopathological alterations. The mechanistic inflammatory expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-ĸB), and expression of caspase-3 protein prominently increased. Zinc supplementation significantly modulated serum liver function markers, antioxidant enzymes, and GSH and MDA levels. Zinc downregulated the expression of cytokines, NO, iNOS, NF-ĸB and caspase-3, and ameliorated histopathological changes. Zinc protects against TAM-induced hepatotoxicity; it may serve as an adjuvant supplement for female patients undergoing TAM chemotherapy.

Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na+), potassium (K+), chloride (Cl-), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Modulatory effects of dietary supplementation by Vernonia amygdalina on high-fat-diet-induced obesity in Wistar rats.

BACKGROUND: Obesity is a growing public health problem arising from energy imbalance. The effect of 10% dietary incorporation of Vernonia amygdalina (VA) leaves into high-fat diets on some biological markers of adiposity and dyslipidaemia was investigated. METHODS: Experimental diets consisted of the following – CD (control diet); HFD (high-fat diet); and HFD- VA (HFD containing 10% Vernonia amygdalina leaves) supplementation. Fifteen male Wistar rats were randomly divided into three groups of five animals each. After twelve weeks of feeding, serum lipid profile, blood glucose concentrations, body weight, adiposity index, feed intake, fecal loss and relative organ weight were investigated. RESULTS: Vernonia amygdalina (VA) inhibited HFD-induced weight gain and adiposity in rats. HFD-induced obese rats showed a significant increase in the levels of serum TG and TC compared to rats on a normal diet. However, the levels of serum TG, TC, LDL-C in HFDVA rats reduced significantly relative to the levels in HFD rats. Our results indicate that HFDVA reversed fatty infiltration leading to decreased body weight and fat tissue mass in the rats. CONCLUSIONS: These results suggested that incorporation of Vernonia amygdalina into high-fat diets may have therapeutic potentials for obesity and related metabolic disorders. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted.

Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats.

BACKGROUND: Methotrexate (MTX) is an efficacious anticancer agent constrained in clinical use due to its toxicity on non-targeted tissue, a considerable source of worry to clinicians. Because the toxicity is associated with oxidative stress and inflammation, the study explored antioxidant and anti-inflammatory effect of virgin coconut oil (VCO) supplementation in nephrotoxicity induced by MTX in rats. METHODS: Rats were randomized into 4 groups (n=6) as follows: Control group; MTX group injected with single dose of MTX (20mg/kg, ip) on day 14; VCO (5%)+MTX and VCO (15%)+MTX groups were pre-treated with VCO diet and injected with single dose of MTX (20mg/kg, ip) on day 14. After 3 days of MTX injection, serum kidney markers, renal activities of antioxidant enzymes and glutathione (GSH) content were determined. Lipid peroxidation level and inflammatory markers- interleukin-6 (IL-6), nitric oxide (NO) and C-reactive protein (CRP) were estimated in kidney. Histopathological alterations were examined for kidney damage. RESULTS: MTX nephrotoxicity was evidenced by markedly elevated serum renal markers along with significant decreases in renal GSH and activities of antioxidant enzymes confirmed by histopathology. Lipid peroxidation level, IL-6, NO and CRP markedly increased compared to control. VCO supplementation prior to MTX injection attenuated MTX-induced oxidative nephrotoxicity via prominent increases in GSH and antioxidant enzyme activities in a dose-dependent manner. The renal inflammatory markers and MDA depleted considerably compared to MTX control group. Histopathological alterations were mitigated to confirm the biochemical indices. CONCLUSION: VCO supplementation demonstrates nephroprotective activity by attenuating MTX oxidative nephrotoxicity via antioxidant and anti-inflammatory activities in kidney. Our results suggested that VCO may benefit cancer patients on MTX chemotherapy against kidney injury.

Haematological and biochemical studies on Justicia carnea leaves extract in phenylhydrazine induced-anemia in albino rats.

BACKGROUND: Justicia carnea is a medicinal plant used widely in Nigeria which is reported to have diverse functions, including blood-boosting potential. Aim. The effect of the ethanol extract of Justicea carnea (JC) leaves in phenylhydrazine induced-anemia albino rats on haematological and lipid profile parameters was investigated. METHODS: The experimental animals were randomly grouped into five groups of six rats each – group 1 (non-anemic control), group 2 (anemic control), group 3 (500 mg/kg of JC extract), group 4 (1000 mg/kg of JC extract) and group 5 (DMSO control). Phenylhydrazine was administered once at a dose of 80 mg/kg b.w.  to induce hemolytic anemia. After 28 days of extract administration, they were humanely sacrificed and the serum collected was used for biochemical analysis. RESULTS: In the acute toxicity study, the LD50 was found to be above 5000 mg/kg body weight. Packed Cell Volume (PCV) values, Red Blood cell (RBC) and haemoglobin (Hb) concentrations decreased (p < 0.05) sig- nificantly after 48 hours of phenylhydrazine induction, but after 28 days of administering extracts of Justicia carnea, PCV values, RBC and Hb increased (p < 0.05) significantly. There were significant (p < 0.05) de- creases in cholesterol, triacylglycerol, and LDL cholesterol concentrations in the extract-administered groups (groups 3&4) relative to the anemic control. There was a significant (p < 0.05) increase in HDL-cholesterol concentrations in the extract groups (3&4) relative to the non-anemic control. CONCLUSIONS: Extracts of Justicia carnea not only reversed anemic conditions in the phenylhydrazine-induced rats, it also improved the lipid profile, and this may be attributed to its rich phytochemical, nutrient and vita- min composition. Therefore, the findings of the study suggest that J. carnea leaves could be used to manage lipid abnormalities associated with anemia.

Virgin coconut oil supplementation attenuates acute chemotherapy hepatotoxicity induced by anticancer drug methotrexate via inhibition of oxidative stress in rats.

BACKGROUND: The emerging health benefit of virgin coconut oil (VCO) has been associated with its potent natural antioxidants; however, the antioxidant and hepatoprotective effect of VCO against methotrexate-induced liver damage and oxidative stress remains unexplored. The study explored the antioxidant and hepatoprotective effects of VCO against oxidative stress and liver damage induced by anticancer drug methotrexate (MTX) in rats. METHODS: Liver damage was induced in Wistar rats pretreated with dietary supplementation of VCO (5% and 15%) by intraperitoneal administration of MTX (20mg/kg bw) on day 10 only. After 12days of treatment, assays for serum liver biomarkers (aminotransferases), alkaline phosphatase, albumin and total protein as well as hepatic content of malondialdehyde, reduced glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were carried out. Liver was used to examine histopathological changes. RESULTS: MTX administration induced significant increase in serum liver enzymes along with marked decrease in albumin and total protein compared to control group. Hepatic activities of antioxidant enzymes were significantly decreased, while malondialdehyde increased significantly. Treatment with VCO supplemented diet prior to MTX administration attenuated MTX-induced liver injury and oxidative stress evidenced by significant improvements in serum liver markers, hepatic antioxidant enzymes and malondialdehyde comparable to control group. Histopathological alterations were prevented and correlated well with the biochemical indices. CONCLUSION: The study suggests antioxidant and hepatoprotective effects of VCO supplementation against hepatotoxicity and oxidative damage via improving antioxidant defense system in rats. Our findings may have beneficial application in the management of hepatotoxicity associated with MTX cancer chemotherapy.

Aqueous and methanol extracts of Vernonia amygdalina leaves exert their anti-obesity effects through the modulation of appetite-regulatory hormones.

CONTEXT: Aqueous and methanol extracts of Vernonia amygdalina Del. (Asteraceae) (AEVA and MEVA, respectively) leaves are reported to possess anti-obesity properties, exerted through unknown mechanisms. OBJECTIVE: This study investigated the effects of AEVA and MEVA on relevant hormones and enzymes in high-fat diet (HFD)-induced obese rats. MATERIALS AND METHODS: Forty-two Wistar rats were placed into seven groups. The test groups received 100 mg/kg.bw AEVA (AEVA100), 500 mg/kg.bw AEVA (AEVA500), 50 mg/kg.bw MEVA (MEVA50) and 200 mg/kg.bw MEVA (MEVA200), respectively. The positive control (PC) group received 20 mg/kg.bw Orlistat, while the negative control (NeC) and normal control (NoC) groups received distilled water. The extracts were given orally daily for 12 weeks. Thereafter, the concentrations/activities of relevant hormones/enzymes in their sera were determined. RESULTS: Insulin concentrations (ng/ml) in the test groups ranged from 1.08 ± 0.01 (AEVA100) to 1.09 ± 0.01 (AEVA500). They were all similar (p > .05) to the NoC and PC controls. Leptin concentrations (pg/ml) in the test rats ranged from 0.02 ± 0.01 (AEVA500) to 0.03 ± 0.00 (MEVA50), and were all similar to the NoC group. The ghrelin concentrations of only the AEVA500 and MEVA200 groups were similar to those of the PC group (0.10 ± 0.01 pg/ml). AEVA100 and MEVA200 resulted in adiponectin concentrations (ng/ml) of the rats (0.27 ± 0.04 and 0.28 ± 0.04 respectively) that were similar to the PC group. The activities of lipoprotein lipase and the concentrations of intestinal amylase in the test rats were similar to values obtained for the control groups. CONCLUSION: Appetite regulation may be the mechanism through which the weight-loss properties of AEVA and MEVA are expressed.