Sodium butyrate arrests pancreato-hepatic synchronous uric acid and lipid dysmetabolism in high fat diet fed Wistar rats.

High fat diet (HFD) is a risk factor for metabolic syndrome which is characterized by overt glucose dysmetabolism and tissue derangement. The liver and pancreas are important metabolic tissues with anatomical proximity sharing splanchnic and mesenteric circulation but it is unclear whether, there is an associated metabolic status between the two organs in health and disease. Uric acid (UA) hypersecretion and ectopic lipid accumulation are characteristic pathophysiology of an array of non-communicable diseases. Sodium butyrate (BUT) is reputed for therapeutic roles in metabolic derangement. Therefore, the present study investigated synchrony in hepatic and pancreatic UA and lipid metabolic status in HFD-induced glucose dysregulation and probed the beneficial effects of BUT. Twenty-four female Wistar rats were treated with normal rat chow and distilled water (po) or sodium butyrate (200 mg/kg; po) or high fat diet and distilled water (po) or high fat diet and sodium butyrate. Results showed that HFD increased plasma, pancreatic and hepatic triglyceride, triglyceride-glucose index, malondialdehyde, uric acid (UA), lactate dehydrogenase but reduced glucose-6-phosphate dehydrogenase. Histological analysis revealed hepatic and pancreatic architectural derangement and cellular degeneration in HFD-fed animals. However, BUT reversed the HFD-induced systemic, pancreatic and hepatic synchronous dysmetabolism with evidence of improved histology. HFD-induced lipid and UA alterations were synchronous in the pancreas and liver. BUT elicits beneficial effects on systemic and tissue HFD-induced deleterious metabolic changes which were synchronized in pancreas and liver of rats.

Suppression of uric acid and lactate production by sodium acetate ameliorates hepatic triglyceride accumulation in fructose-insulin resistant pregnant rats.

High fructose intake has been associated with perturbed lipid, uric acid and lactate homeostasis. However, consumption of fructose-sweetened beverages is not usually regulated during pregnancy. The effect of short-chain fatty acid (acetate) on the metabolic effects of high fructose intake during pregnancy is not known. We hypothesized that acetate prevents gestational fructose-induced hepatic triglyceride (TG) accumulation by suppressing uric acid and lactate production. Pregnant Wistar rats were randomly separated into three groups (n = 6/group) receiving drinking water (CON), 10 % (w/v) fructose drink (FRU) and 10 % (w/v) fructose with 200 mg/kg (w/w; p.o.) sodium acetate (FRU + ACE) daily for nineteen days. Fructose intake resulted in increased body weight gain, liver weight, fluid intake, visceral fat, insulin resistance, fasting blood glucose, insulin, plasma and hepatic TG, total cholesterol, free fatty acid, lipid peroxidation, adenosine deaminase, xanthine oxidase, uric acid, lactate, lactate dehydrogenase, and liver injury marker enzymes. However, gestational high fructose intake led to depressed plasma and hepatic glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant barrier, adenosine and food intake. All these effects except water intake and food intake were abated by sodium acetate. These results demonstrate that maternal fructose-enriched drink would cause hepatic TG accumulation that is associated with perturbed glucose, uric acid, lactate homeostasis, and G6PD-dependent antioxidant barrier. These results also demonstrate that acetate protects the liver against gestational fructose-induced TG accumulation by inhibiting uric acid and lactate production. Thus, acetate may be useful in the treatment of hyperuricemia- and hyperlactatemia-related disorders.

Triglyceride/HDL-cholesterol ratio and plasminogen activator inhibitor-1 independently predict high pulse pressure in sickle cell trait and disease.

We hypothesised that TG/HDL-C ratio and PAI-1 would be associated with high pulse pressure (PP) in young adults with sickle cell trait (SCT) and sickle cell disease (SCD). We compared the clinical, biochemical, and cardiometabolic parameters among individuals with normal genotype (HbAA; n = 60), SCT (HbAS; n = 60), and SCD (HbSS; n = 60), all in steady state. Using multivariate linear regression analysis, high PP was positively related to TG/HDL-C ratio in SCT (ß = 0.307; p = .014) and PAI-1 (ß = 0.499; p = .001) in SCD. The curve of receiver operating characteristic also showed that TG/HDL-C ratio and PAI-1 are efficient predictors of high PP in SCT carriers and SCD patients, respectively. This study suggests that increased levels of TG/HDL-C ratio and PAI-1 may be salient risk factors that would promote the development of arterial stiffness and other CVD in SCT carriers and SCD patients.

Very low dose spironolactone protects experimentally-induced polycystic ovarian syndrome from insulin-resistant metabolic disturbances by suppressing elevated circulating testosterone.

Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women of reproductive age and hyperandrogenism is a prominent feature of PCOS resulting in infertility and increased risk of developing metabolic disorders including insulin resistance (IR), abdominal adiposity, glucose intolerance and cardiovascular diseases. Spironolactone (SPL), a non-selective mineralocorticoid receptor (MR) antagonist, has been in wide clinical use for several decades. In this study, we investigated the effects of SPL on IR and metabolic disturbances in letrozole-induced PCOS rats. Eighteen adults female Wistar rats were randomly divided into 3 groups and treated with vehicle, letrozole (LET; 1 mg/kg) and LET + SPL (SPL; 0.25 mg/kg), p.o. once daily for 21 consecutive days. Results showed that LET treatment induced PCOS characterised by elevated plasma testosterone and luteinizing hormone (LH) accompanied with increased body weight and visceral adiposity, IR, glucose intolerance, dyslipidemia and altered histomorphological ovaries. Treatment with SPL however attenuated the elevated testosterone in LET-induced PCOS model accompanied with a reversal in all the observed alterations. Taken together, analysis of the physical, biochemical and histological evidences shows that the protective effect of this very low dose spironolactone may be through its anti-androgenic mechanism.

Ameliorative effect of low-dose spironolactone on obesity and insulin resistance is through replenishment of estrogen in ovariectomized rats.

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but the reverse is the case after menopause, indicating a possible protective effect of estrogen on cardiometabolic function. Although various hormonal therapies have been formulated to combat the CVD risks in postmenopausal state, the beneficial effects have not been consistent. Obesity with insulin resistance (IR) is closely linked to CVD risks while ovariectomized rodents have been shown to mimic a state of obesity and IR. We therefore hypothesized that low-dose spironolactone would ameliorate obesity and IR in estrogen-deprived rats by replenishing estrogen and suppressing elevated glycogen synthase kinase-3 (GSK-3). Ten-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM), spironolactone (SPL; 0.25 mg/kg), and ovariectomized (OVX) rats treated with or without spironolactone daily for 8 weeks. Results showed that estrogen deprivation through ovariectomy caused increased body mass gain and visceral adiposity that are accompanied by increased HOMA-IR, HOMA-ß, 1-hour postload glucose, glucose intolerance, platelet/lymphocyte ratio, plasma insulin, atherogenic dyslipidemia, uric acid, GSK-3, corticosterone, and aldosterone and depressed 17ß-estradiol. However, treatment of OVX rats with spironolactone ameliorated all these effects. Taken together, the results demonstrate that treatment with low-dose spironolactone improves obesity and IR, which appears to involve replenishment of estrogen and suppression of GSK-3 along with circulating mineralocorticoid and glucocorticoid. The findings imply a positive cardiometabolic effect of low-dose spironolactone usage in estrogen-deprived conditions.

Neck circumference is independently associated with relative systemic hypertension in young adults with sickle cell anaemia.

BACKGROUND: A seemingly interesting observation in patients with sickle cell anaemia (SCA) is that they usually have lower systemic blood pressures (BP) and insulin resistance than persons in the general population in spite of chronic inflammation and vasculopathy. However, relative systemic hypertension (rHTN) has been linked to pulmonary hypertension, increased blood viscosity and renal insufficiency, which could indicate a risk of developing cardiometabolic disorder (CMD) in SCA.We therefore hypothesized that neck circumference (NC) and CMD marker; triglyceride glucose (TyG) index would independently predict rHTN in young adults with SCA in steady state. METHODS: We compared the anthropometrical, hematological, hemorheological and CMD markers between SCA patients with normal BP < 120/70 mmHg; nHTN, n = 65) and those with rHTN (BP ≥ 120/70 mmHg, n = 32). RESULTS: Our results showed that SCA with rHTN had significantly higher body weight, waist circumference, NC, plasma viscosity, systolic and diastolic BP. Results also indicated that NC (OR: 2.98; 95% CI 1.46 to 6.10, p < 0.01) was a predictor of rHTN in SCA independent of gender, age, weight, waist circumference, BMI, blood viscosity, triglyceride or TyG. A receiver operating characteristic curve analysis also showed that NC was the most efficient predictor of rHTN than other CMD markers. CONCLUSION: The present study demonstrates that increased NC is a salient risk factors that is independently associated with rHTN in SCA. The finding therefore underscores the utility of NC in early detection and stratification of systemic hypertension, particularly in individuals with SCA.

Oral hormonal therapy with ethinylestradiol-levonorgestrel improves insulin resistance, obesity, and glycogen synthase kinase-3 independent of circulating mineralocorticoid in estrogen-deficient rats.

Estrogen deficiency has been associated with increased incidence of cardiovascular diseases , and recent clinical trials of standard formulations of hormonal therapies have not demonstrated consistent beneficial effects. Estrogen-progestin therapy has been used as exogenous estrogen to normalize depressed estrogen level during menopause. Ovariectomized rodents mimic an estrogen-deficient state in that they develop cardiometabolic dysfunction, including insulin resistance (IR). We therefore hypothesized that hormonal therapy with combined oral contraceptive steroids, ethinylestradiol-levonorgestrel (EEL), improves IR, obesity, and glycogen synthase kinase-3 (GSK-3) through reduction of circulating mineralocorticoid in ovariectomized rats. Twelve-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM) and ovariectomized (OVX) rats were treated with or without EEL (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel) daily for 8 weeks. Results showed that OVX or SHM + EEL treated rats had increased HOMA-IR (homeostatic model assessment of IR), 1 h postload glucose, HOMA-ß, triglycerides (TG), total cholesterol (TC), TC/HDL cholesterol, TG/HDL cholesterol, plasma insulin, GSK-3, corticosterone, and aldosterone. On the other hand, OVX + EEL treatment ameliorated all these effects except that of aldosterone. Taken together, the results demonstrate that oral hormonal replacement with EEL improves IR and pancreatic ß-cell function and suppresses GSK-3 and glucocorticoid independent of circulating aldosterone, suggesting a positive cardiometabolic effect of oral EEL therapy in estrogen-deficient rats.

Low-dose spironolactone ameliorates insulin resistance and suppresses elevated plasminogen activator inhibitor-1 during gestational testosterone exposure.

CONTEXT: Elevated gestational circulating testosterone has been associated with pathological pregnancies that increase the risk of development of cardiometabolic disorder in later life. OBJECTIVE: We hypothesised that gestational testosterone exposure, in late pregnancy, causes glucose deregulation and atherogenic dyslipidaemia that would be accompanied by high plasminogen activator inhibitor-1 (PAI-1). The study also hypothesise that low-dose spironolactone treatment would ameliorate these effects. METHODS: Pregnant Wistar rats received vehicle, testosterone (0.5 mg/kg; sc), spironolactone (0.5 mg/kg, po) or testosterone and spironolactone daily between gestational days 15 and 19. RESULTS: Gestational testosterone exposure led to increased HOMA-IR, circulating insulin, testosterone, 1-h post-load glucose, atherogenic dyslipidaemia, PLR, PAI-1 and MDA. However, all these effects, except that of circulating testosterone, were ameliorated by spironolactone. CONCLUSIONS: These results demonstrate that low-dose spironolactone ameliorates glucose deregulation and atherogenic dyslipidaemia during elevated gestational testosterone exposure, at least in part, by suppressing elevated PAI-1.

Analgesic and anti-inflammatory effects of aqueous extract of Zea mays husk in male Wistar rats.

The analgesic and anti-inflammatory activities of Zea mays husk extract (25, 50, 100, and 200 mg/kg of body weight) were investigated in rats. The hot plate and formalin-induced paw licking models were used to assess analgesic effects of the extract, whereas the carrageenan and cotton pellet models were used for the evaluation of anti-inflammatory activity. The extract at 25, 50, 100, and 200 mg/kg body weight significantly (P < .05) reduced pain stimuli and inflammatory activity when compared with the control group. The reductions in paw licking time and granuloma weight in the formalin and cotton pellet models were both dose dependent. Also, the 200 mg/kg doses of the extract produced higher effects compared with indomethacin (5 mg/kg body of weight) in all the tests. These observations suggest that Z. mays husk extract may have analgesic and anti-inflammatory effects that may be due to its tannins and polyphenolic constituents. These results provide scientific validation for the use of Z. mays husk decoction for the treatment of pain and inflammatory conditions in Nigerian folk medicine.

High-calcium diet reduces blood pressure, blood volume and preserves vasorelaxation in oral contraceptive-treated female rats.

Cardiovascular complications are the major clinical challenges among users of synthetic steroids in oral contraceptive (OC) formulations. Interventions that reduce blood volume and improve vasorelaxation have been shown to reduce hypertension and the associated risk factors. The aim of the present study was to investigate the influence of increasing dietary calcium from 0.9 to 3.0% on the development of OC-induced high blood pressure and associated changes in female Sprague-Dawley rats treated with a combination of OC steroids (1 microg ethinyl estradiol and 10 microg norgestrel; p.o.) daily for 10 weeks. Results showed that OC administration led to significant increases in blood pressure, blood volume and cardiac weight. Conversely, OC caused significant reductions in body weight, urinary excretion of water, plasma levels of calcium, 17beta-estradiol and progesterone. Increased dietary calcium attenuated the elevation in blood pressure induced by OC and abrogated the associated changes in blood volume, cardiac weight, plasma calcium and urinary excretion of water. The endothelium-dependent relaxation responses to acetylcholine and endothelium-independent relaxation responses to sodium nitroprusside in noradrenaline-precontracted aortic rings were not significantly different among the groups. The results indicate that increased calcium intake abrogated the development of high blood pressure and associated increased blood volume and cardiac weight during OC treatment. The beneficial effect of increased dietary calcium during OC use may be explained by improved diuretic and preserved vasorelaxant responses.

Studies on the analgesic, anti-inflammatory and antipyretic effects of Parquetina nigrescens leaf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Parquetina nigrescens is a shrub that is commonly used in different parts of West Africa for the treatment of several ailments which includes pain, fever and inflammatory conditions. AIM OF THE STUDY: The present study was designed to investigate the analgesic, anti-inflammatory and antipyretic effects of the aqueous extract of Parquetina nigrescens leaves in rats. MATERIALS AND METHODS: Five groups were used for each study, groups 1 and 5 served as control (saline) and reference (indomethacine) respectively, while groups 2-4 received the extract (50-200 mg/kg) orally. Formalin paw licking and hot plate latency tests were used for analgesic studies. Carrageenan oedema, cotton pellet granuloma and formaldehyde arthritis models were used to quantify the anti-inflammatory activities while the brewer's yeast was used for inducing pyrexia. RESULTS: The results of the analgesic study show that the extract produced significant (p<0.05) analgesia in the hot plate and in the formalin tests. In the anti-inflammatory study, Parquetina nigrescens produced significant (p<0.05) inhibition of the various types of inflammation. The extract also inhibited the pyrexia induced by brewer's yeast. CONCLUSION: The result justifies the traditional uses of Parquetina nigrescens for the treatment of fever, inflammatory and painful conditions.

Anti-inflammatory activities of ethanolic extract of Carica papaya leaves.

The anti-inflammatory activity of an ethanolic extract of Carica papaya leaves was investigated in rats using carrageenan induced paw oedema, cotton pellet granuloma and formaldehyde induced arthritis models. Experimental animals received 25-200 mg/Kg (orally) of the extracts or saline (control group) and the reference group received 5 mg/ Kg of indomethacin. The ulcerogenic activity of the extract was also investigated. The results show that the extracts significantly (p <0.05) reduced paw oedema in the carrageenan test. Likewise the extract produced significant reduction in the amount of granuloma formed from 0.58 +/-0.07 to 0.22 +/-0.03 g. In the formaldehyde arthritis model, the extracts significantly reduced the persistent oedema from the 4th day to the 10th day of the investigation. The extracts also produced slight mucosal irritation at high doses. The study establishes the anti-inflammatory activity of Carica papaya leaves.

Effect of increased dietary calcium on hemorheological, lipid and lipid peroxidation in oral contraceptive-treated female rats.

Oral contraceptive (OC) steroids use has been associated with variable effects on blood lipid and rheological properties, and abnormal plasma lipid and hemorheological profiles has been shown to be in almost all conditions associated with accelerated atherosclerotic cardiovascular disorders. This study aimed at investigating the effect of increased calcium intake on plasma levels of lipids, malondialdehyde (lipid peroxidation index), free radical defense system and hemorheological variables in OC-treated female Sprague-Dawley rats. OC-treated and OC + Calcium-treated groups received a combination of ethinyl estradiol and norgestrel for 10 weeks by oral gavage. OC + Calcium-treated rats fed on 2.5% calcium diet while other groups fed on 0.9% calcium diet in addition to drinking water ad libitum. Results showed that LDL-cholesterol, total cholesterol/HDL-cholesterol ratio, LDL-cholesterol/HDL-cholesterol ratio, plasma viscosity, hematocrit and plasma fibrinogen were significantly higher while plasma HDL-cholesterol, 17beta-estradiol, testosterone and calcium levels were significantly lower in OC-treated rats when compared with the control rats. The altered plasma lipid and calcium levels were prevented by increased calcium intake, whereas the OC-induced changes in hematocrit, plasma viscosity, fibrinogen, 17beta-estradiol and testosterone were not affected by increased dietary calcium. Plasma lipid peroxidation index, ascorbic acid and albumin levels were comparable in all the groups. The present study demonstrated that OC-induced altered blood lipid and rheological properties were not associated with increased lipid peroxidation. The results also suggest that calcium enriched diet may improve lipid profile but not hemorheological parameters, by a mechanism that is independent of circulating 17beta-estradiol and testosterone in OC-treated rats.

Anti-inflammatory activity of aqueous leaf extract of Chromolaena odorata.

The anti-inflammatory activity of the aqueous extract of Chromolaena odorata was investigated in rats using the carrageenan-induced oedema, cotton pellet granuloma and formalin-induced oedema methods. The extract was administered orally at doses of 25, 50, 100 and 200 mg/kg. In the carrageenan method the paw oedema was significantly reduced by all the doses of the extract administered, with the 200 mg/kg dose producing the highest oedema inhibition (80.5%). In the cotton pellet method, granuloma weight was significantly reduced from 14 +/- 0.1 to 9.0 +/- 0.1 mg, while in the formaldehyde induced arthritis the extract inhibited the oedema during the 10-day period. In conclusion, this study has established the anti-inflammatory activity of C. odorata and, thus, justifies the traditional uses of the plant in the treatment of wounds and inflammation.

Analgesic and anti-inflammatory properties of Nelsonia canescens leaf extract.

An ethanolic extract of the dried leaves of Nelsonia canescens was investigated for anti-inflammatory and analgesic activities in rat. In the test for anti-inflammatory activity, the extract at the doses of 50-200 mg/kg significantly (P<0.05) inhibited carrageenan-induced paw oedema and cotton pellet granuloma. Likewise, at the same doses the extract exhibited analgesic activity in both the hot plate latency assay (hot plate maintained at 55 degrees C) and on the early and late phases of formalin-induced paw licking in rats. The result of the present study confirm that Nelsonia canescens has analgesic and anti-inflammatory activities. These findings also justify the traditional use of the plant for treating pain.

Studies on the anti-inflammatory and analgesic properties of Tithonia diversifolia leaf extract.

A methanol extract of the dried leaves of Tithonia diversifolia was investigated for anti-inflammatory and analgesic activities. The extract (50-200 mg/kg, p.o.) produced dose-related inhibition of carrageenan-induced paw oedema and cotton pellet-induced granuloma in rats. At the same doses, analgesic effect was also observed with hot plate latency assays maintained at (55 degrees C) as well as on the early and late phases of formalin-induced paw licking in rats. The results of the present study further confirm the use of Tithonia diversifolia traditionally for the treatment of painful inflammatory conditions.