Morin hydrate downregulates inflammation-mediated nitric oxide overproduction and potentiates antioxidant mechanism against anticancer drug doxorubicin oxidative hepatorenal toxicity in rats.

Objective: Doxorubicin (DOX) is a frontline antineoplastic drug that kills cancer cells through genotoxic mechanism; however, it induces organ toxicities. This study assayed whether morin hydrate (MOH) could abrogate DOX hepatorenal toxicity in rats. Materials and Methods: There were 4 groups of rats: Control, MOH, DOX and MOH + DOX. Rats were administered MOH (orally, 100 mg/kg bw) for 7 consecutive days, while DOX was injected (40 mg/kg, ip) on the 5th day only. Hepatorenal function markers, and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were estimated in both organs. Hepatorenal glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels were estimated with histopathology. Results: DOX significantly (p<0.05) reduced antioxidant enzyme activities and GSH level, while NO and MDA levels increased (p<0.05) compared to the control. DOX prominently altered hepatorenal indices and induced histopathological alterations. MOH abrogated the DOX hepatorenal toxicity and alleviated the histological lesions in the liver and kidney. Conclusion: MOH restored the indices via antioxidant mechanism and downregulation of NO overproduction in rats.

Ginger juice prevents cisplatin-induced oxidative stress, endocrine imbalance and NO/iNOS/NF-κB signalling via modulating testicular redox-inflammatory mechanism in rats.

The off-target testicular toxicity of the anticancer drug, cisplatin, is a current clinical concern and worrisome to male cancer patients. Growing evidence has implicated oxidative stress and inflammation in cisplatin toxicity. We have explored whether fresh ginger juice could mitigate testicular toxicity induced by anticancer drug cisplatin in rats. Rats were subjected to oral administration of fresh ginger juice (5 ml/kg body weight/day) for 5 days against testicular damage induced by single ip injection of cisplatin (CIS) (10 mg/kg body weight) on day 2 only. Testicular activities of antioxidant enzymes, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), inflammatory cytokines, inducible nitric oxide synthase (iNOS) and nuclear factor-ĸB (NF-ĸB) and serum hormone levels were estimated. CIS-induced prominent decreases in antioxidant enzyme activities, GSH and serum hormone levels, whereas levels of MDA, cytokines, NO, iNOS and NF-ĸB increased remarkably (p < .05) compared to control. Interestingly, the CIS-induced testicular alterations were considerably mitigated by the fresh ginger juice via abrogation of oxidative stress and anti-inflammatory mechanism. The study suggests, for the first time, antioxidant and anti-inflammatory effects of ginger juice against CIS testicular damage. Fresh ginger juice may have beneficial health impact on testicular side effect of CIS chemotherapy.

Nephroprotective activity of virgin coconut oil on diclofenac-induced oxidative nephrotoxicity is associated with antioxidant and anti-inflammatory effects in rats.

OBJECTIVE: Diclofenac is a non-steroidal anti-inflammatory drug linked with considerable organ toxicity caused via increased generation of reactive oxygen species. We evaluated whether the antioxidant effect of virgin coconut oil (VCO) could prevent diclofenac-induced oxidative nephrotoxicity in rats. MATERIALS AND METHODS: Randomized rats were pre-supplemented orally with VCO (5 or 10 ml/kg body weight) from day 1 to 24, and injected with normal saline or diclofenac (100 mg/kg) from day 22 to day 24 intraperitoneally. RESULTS: Diclofenac significantly (p<0.05) increased serum urea and creatinine levels. Renal tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels markedly (p<0.05) increased, whereas renal glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activities considerably (p<0.05) decreased compared to normal control. Histopathological alterations were caused by diclofenac. However, treatment with oral VCO for 21 days prior to diclofenac administration, attenuated histological renal damage, and restored antioxidant enzyme activities and TNF-α levels in kidney. CONCLUSION: These findings revealed that VCO has potential benefits to prevent diclofenac-induced nephrotoxic damage.

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.

Beauty and the Body of the Beholder: Raters' BMI Has Only Limited Association with Ratings of Attractiveness of the Opposite Sex.

OBJECTIVE: Assortative mating for adiposity increases the genetic burden on offspring, but its causes remain unclear. One hypothesis is that people who have high adiposity find other people with obesity more physically attractive than lean people. METHODS: The attractiveness of sets of images of males and females who varied in adiposity were rated by opposite sex subjects (559 males and 340 females) across 12 countries. RESULTS: There was tremendous individual variability in attractiveness ratings. For female attractiveness, most males favored the leanest subjects, but others favored intermediate fatness, some were indifferent to body composition, and others rated the subjects with obesity as most attractive. For male images rated by females, the patterns were more complex. Most females favored subjects with low levels of adiposity (but not the lowest level), whereas others were indifferent to body fatness or rated the images depicting individuals with obesity as the most attractive. These patterns were unrelated to rater BMI. Among Caucasian males who rated the images of the thinnest females as being more attractive, the magnitude of the effect depended on rater BMI, indicating limited "mutual attraction." CONCLUSIONS: Individual variations in ratings of physical attractiveness were broadly unrelated to rater BMI and suggest that mutual attraction is an unlikely explanation for assortative mating for obesity.

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.