Epigallocatechin-3-gallate in combination with corticosteroids mitigates heat stress-induced acute kidney injury through modulating heat shock protein 70 and toll-like receptor 4-dependent pathways.

Recently, recurrent heat stress (HS) and dehydration have been exhibited to give rise to kidney disease epidemic in hot regions. The current study was carried out to estimate a possible renoprotective effect of dexamethasone (Dexa) and epigallocatechin-3-gallate (EGCG) as a heat shock protein (HSP)-70 inhibitor on HS-induced nephropathy. In total, five groups of rats were used: control group, HS group (exposed to heat for 40 min), Dexa+HS group (rats were injected with Dexa i.p.15 mg/kg/day for 3 days followed by HS), EGCG+HS group (rats received EGCG 100 mg/kg/day, orally, for 7 days followed by HS), and EGCG+ Dexa +HS group (rats received EGCG 100 mg/kg/day, orally, for 7 days and injected Dexa as described along the last 3 days followed by HS). Kidney sections were stained with H&E and scored for tubular injury. A marked increase in creatinine, urea, malondialdehyde (MDA), monocyte chemoattractant protein (MCP)-1, HSP-70, nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR-4) and Caspase-3 expression was observed after HS induction (p < 0.001). Treatment with EGCG combined with Dexa notably reduced tubular injury, MCP-1, HSP-70, NF-κB, and TLR-4 levels (p < 0.001). Moreover, it increased IL-10, antioxidant capacity and Bcl-2 expression levels in the kidney (p < 0.001). This renoprotective impact might be attributed to anti-inflammatory, antioxidant, and anti-apoptotic mechanisms besides interfering with TLR-4-mediated NF-κB activation pathway.

Gum Acacia mitigates diclofenac nephrotoxicity by targeting monocyte chemoattractant protein-1, complement receptor-1 and pro-apoptotic pathways.

Treatment of many inflammatory diseases involves a chronic use of NSAIDs in large doses increasing acute kidney injury risk. This study was designed to evaluate a potential renoprotective effect of Gum Acacia (GA) on diclofenac (DICF) induced nephrotoxicity. Six groups of rats were used: normal group; control group (deprived from water during week 13), DICF group (deprived from water during week 13 and injected DICF i.p. 15 mg/kg/12 h at days 4 through 6 of water deprivation days, GA groups (1, 2 or 3 g/kg/day in drinking water) for 12 weeks followed by water deprivation and DICF injection as described. Kidney function, oxidative stress and anti-oxidant biomarkers were measured. Interleukin-1ß, IL-10, TNF-α, complement receptor (CR)-1, monocyte chemoattractant protein (MCP)-1 and caspase-3 were assessed. Kidney sections were scored for fibrosis, tubular injury and inflammatory cells. An elevation in renal biomarkers, inflammatory cytokines, malondialdehyde and apoptotic markers was observed after DICF injection (p < 0.001). Gum Acacia (mostly 3 g/kg) markedly reduced fibrosis, tubular injury, IL-1ß, TNF-α, caspase-3 and MCP-1 levels (p < 0.01). It increased IL-10, anti-oxidant capacity, CR-1 level in the kidney (p < 0.001). Protective effect may be mediated by antioxidant, anti-inflammatory and anti-apoptotic mechanisms besides interfering with monocytes and complement mediated tissue damage pathways.

The Falconoid Luteolin Mitigates the Myocardial Inflammatory Response Induced by High-Carbohydrate/High-Fat Diet in Wistar Rats.

Luteolin is a major component of many medicinal plants and traditional medicines. The current study aims at testing its protective effect against high-carbohydrate/high-fat (HCHF) diet-induced cardiac dysfunction in rats. Male Wistar rats were divided into six groups as follows: control group that received standard rat chow, group received HCHF diet (~ 30% carbohydrate and 42% fat) daily for 16 weeks, and four groups received HCHF diet concurrently with luteolin (10, 25, 50 or 100 mg/kg; 10% w/v suspension in 0.9% NaCl) daily from the first week by oral gavage. Body weight was measured weekly. At the end of the study, histopathological examinations of stained heart sections were carried out. Lipid profile, oxidative stress, and cardiac function biomarkers were measured. Furthermore, neurohumoral mediators and inflammatory cytokines (TNF-α, IL-18) were assigned. Results showed a significant improvement in cardiac function, tissue integrity, and a decrease in the compensatory neurohumoral mediators by luteolin 50 and 100 mg/kg. In addition, a significant (P < 0.05) decrease in collagen deposition, fibrosis percentage, lipid peroxidation, and inflammatory cells (macrophages and lymphocytes) infiltration was observed. Tested doses of luteolin decreased lipid peroxidation and elevated the endogenous antioxidant biomarkers (reduced glutathione and superoxide dismutase) significantly (P < 0.05). Finally, luteolin decreased TNF-α and IL-18 (P < 0.001) in a dose-dependent manner. It can be concluded that luteolin has a cardioprotective effect against HCHF diet-induced myocardial inflammation through antioxidant anti-inflammatory mechanisms.

Modified citrus pectin stops progression of liver fibrosis by inhibiting galectin-3 and inducing apoptosis of stellate cells.

Modified citrus pectin (MCP) is a pH modified form of the dietary soluble citrus peel fiber known as pectin. The current study aims at testing its effect on liver fibrosis progression. Rats were injected with CCl4 (1 mL/kg, 40% v/v, i.p., twice a week for 8 weeks). Concurrently, MCP (400 or 1200 mg/kg) was administered daily in drinking water from the first week in groups I and II (prophylactic model) and in the beginning of week 5 in groups III and IV (therapeutic model). Liver function biomarkers (ATL, AST, and ALP), fibrosis markers (laminin and hyaluronic acid), and antioxidant biomarkers (reduced glutathione (GSH) and superoxide dismutase (SOD)) were measured. Stained liver sections were scored for fibrosis and necroinflammation. Additionally, expression of galectin-3 (Gal-3), α-smooth muscle actin (SMA), tissue inhibitor metalloproteinase (TIMP)-1, collagen (Col)1A1, caspase (Cas)-3, and apoptosis related factor (FAS) were assigned. Modified pectin late administration significantly (p < 0.05) decreased malondialdehyde (MDA), TIMP-1, Col1A1, α-SMA, and Gal-3 levels and increased levels of FAS, Cas-3, GSH, and SOD. It also decreased percentage of fibrosis and necroinflammation significantly (p < 0.05). It can be concluded that MCP can attenuate liver fibrosis through an antioxidant effect, inhibition of Gal-3 mediated hepatic stellate cells activation, and induction of apoptosis.

Yogurt Containing the Probacteria Lactobacillus acidophilus Combined with Natural Antioxidants Mitigates Doxorubicin-Induced Cardiomyopathy in Rats.

Probiotics and antioxidants have a definite improving effect in cardiovascular diseases. This study aims at mitigating doxorubicin toxicity on cardiac function through consuming a functional food. Five groups of adult male Sprague-Dawley rats were used along 22 weeks. Group I received 30 g/kg/day food enriched with yogurt, green tea extract, and carrots (80, 0.84, and 100 g/kg diet, respectively) from the first week, group II received carvedilol 30 mg/kg/day orally from week 17, group III received both carvedilol and tested food, and groups IV and V were +ve and -ve control groups, respectively. In week 17, cardiomyopathy was induced by i.p. injection of 2.5 mg/kg doxorubicin every 48 h for 2 weeks. Histopathological and electrophysiological examinations and biochemical analysis were done. Lipid peroxidation, antioxidant effect, heart failure compensatory mediators, and proinflammatory cytokines were assessed. Tested food normalized time between the start of Q wave and the end of T wave on electrocardiogram (QT interval) and heart rate compared to the doxorubicin group (P<.05). It also improved hypertrophy indicated by a significant (P<.05) decrease in heart/body weight ratio, angiotensin-II (Ang-II), and atrial natriuretic peptide (ANP) serum levels. Histopathological examination of cardiac sections from the tested food group revealed less marked vacuolization and low perivascular fibrosis percentage (0.7803 ± 0.04). A significant (P<.001) decrease in serum creatine kinase-membrane bound, lactate dehydrogenase, triglycerides, cholesterol, low-density lipoprotein cholesterol, and tissue malondialdehyde (MDA) levels was observed in addition to an increase in serum Na(+)/K(+) ATP1A1 and cardiac reduced glutathione (GSH) levels. Tested food also lowered the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) serum levels significantly (P<.01). Probiotic food containing Lactobacillus acidophilus, green tea, and carrots can improve membrane integrity and cardiac contractility in doxorubicin-induced cardiomyopathy by decreasing TNF-α, IL-6, MDA, increasing GSH, and modulating compensatory mediators such as Ang-II and ANP.