Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1

<p>Abstract</p> <p>Background</p> <p>Aflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver.</p> <p>Methods</p> <p>Adult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks.</p> <p>Results</p> <p>Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2.</p> <p>Conclusion</p> <p>We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.</p

Cardiac Ameliorative Effect of Moringa oleifera Leaf Extract in High-Fat Diet-Induced Obesity in Rat Model

The consumption of a high-fat diet is linked to the development of obesity and considered a risk factor for cardiovascular diseases. The aim of this study was to evaluate the effect of the methanolic extract of Moringa oleifera leaves (MEML) on the high-fat diet- (HFD-) induced obesity and cardiac damage in rats. MEML, at a dose of 200 mg/kg/bw and 400 mg/kg/bw, was orally administrated to obese rats for 12 weeks. M. oleifera leaves were proved to be rich in nutrients and minerals. Diversity of phenolic compounds in MEML was evidenced via LC-ESI-MS analysis. The chronic administration of HFD in rats led to an increase in the body weight gain, total cholesterol, and triglycerides and reduction in the HDL-C levels. The obtained results indicated a significant increase (p<0.05) in the cardiac marker enzyme level in obese rats. A significant decrease (p<0.05) in the levels of cardiac catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities was accompanied with an increase of malondialdehyde (MDA) level in the high-fat diet group when compared to those of the control. The treatment with the MEML alleviated abnormalities in the serum biochemical parameters, balanced the antioxidant status, and reestablished the normal histological structure of the heart especially in the case of the higher concentration. Moringa oleifera leaves may be a promising candidate in the management of obesity and its related complications such as heart problems

Extracellular matrix remodelling in rat heart in an unpredictable chronic mild stress model associated with diabetes

630-639The coexistence of depression and diabetes is a serious challenge in cardiovascular disease. However, extracellular matrix (ECM) under stress model associated or not with diabetes remains unknown. This study aims to investigate the involvement of diabetes and unpredictable chronic mild stress (UCMS) on ECM remodelling. Rats were exposed to UCMS, diabetes or combined treatment. mRNA expression of matrix metalloproteinases (MMP-2 and MMP-9), plasminogen activator (t-PA) and inhibitor (PAI-1) was examined by Q-RT-PCR. ECM was determined by ELISA. MMP-2 and MMP-9 mRNA was lower in diabetes (P <0.05). UCMS increased MMP-2 and MMP-9 compared to control and diabetic group. Compared to the control and diabetes groups, MMP-2 and MMP-9 mRNA was significantly increased in the combined treatment group. UCMS increased MMP-2 expression in the diabetic group (P <0.01). Compared to control, gelatinase activity was higher in diabetes and UCMS (P <0.05). Combined diabetes and UCMS significantly increased gelatinase activity compared to T2D and UCMS groups. Collagen, hydroxyproline and fibronectin content were significantly increased in diabetes and combined groups. UCMS combined with diabetes exacerbated diabetes-induced MMPs and fibronectin deposition. In conclusion, comorbidity between diabetes and UCMS may exacerbate ECM remodelling. These findings will be useful in understanding diabetes-induced cardiovascular disease

Combined diabetes and chronic stress exacerbates cytokine production and oxidative stress in rat liver and kidney

AbstractInflammatory response and oxidative stress state have been largely described in diabetes and depression separately but not in combination. We aimed to explore the involvement of diabetes and unpredictable chronic mild stress (UCMS) separately or in combination on inflammatory response and oxidative stress. Diabetes, UCMS or combined rat models were used. Proinflammatory cytokines, Interleukin 6 (IL-6) and Tumor necrosis factor alpha (TNF-α) were assessed by real time quantitative polymerase chain reaction (q-PCR) and Enzyme-Linked Immunosorbent Assay (ELISA). Superoxide dismutase (SOD) and catalase (CAT) were determined by colorimetric assays. In the diabetes group, IL-6 mRNA expression increased by 55% and 34% (p < 0.05), respectively, in liver and kidney. UCMS alone or in combination with diabetes increased the mRNA of IL-6, respectively, by 85% and 78% in the liver and by 28% and 63% in the kidney (p < 0.01 for all). ELISA showed that diabetes and UCMS act in synergy on TNF-α and IL-6 expression. Diabetes and UCMS separately or in combination inhibited significantly (p < 0.01) the activities of the two anti-oxidant enzymes when compared to controls. The malondialdehyde (MDA) level was significantly enhanced in the group with diabetes combined with UCMS compared to UCMS alone in both organs. UCMS enhances the proinflammatory cytokines release and induces oxidative stress imbalance, and diabetes comorbidity with depression aggravates the inflammatory response and lipid peroxidation. These observations can be useful to better understand depression-induced organ damage

Effects of Lupinus luteus on hepatic and renal extracellular compounds turnover under diabetes in rat

Abstract Hepatic and renal extracellular matrix (ECM) turnover associated with diabetes and potential beneficial effects of yellow lupin extract (YLE) need further investigations. The aim of this study was to explore the effect of yellow Lupinus luteus extract (YLE) on renal and hepatic ECM under diabetes. Composition of YLE performed by LC‐ESI‐MS. Diabetes (DM) was induced in rats by alloxan (250 mg/kg, ip). Normal and diabetic rats received 100 mg/kg of YLE for 1 month. ECM was assessed by ELISA. Gelatinases and collagenases were analyzed by a colorimetric assay. Histology was performed on sections of liver and kidney. In the liver, diabetes increases collagen, laminin, and fibronectin contents, respectively, by 49% (p < .01), 56% (p < .01), and 67% (p < .05) compared to control rats. In the kidney, total collagen and laminin contents were increased by 91% (p < .01) and 35% (p < .01) in the DM group, while fibronectin content in diabetic animals and those treated with YLE remains similar to the control group. Collagenases and gelatinases activities were significantly increased by diabetes in liver and kidney. While YLE treatment abrogates diabetes‐enhanced MMPs activities in liver. In diabetic rats, the liver shows signs of diffuse dilatation of the sinusoid veins and steatosis. However, the liver of diabetic rats treated with yellow lupine extract showed a normal histological aspect similar to controls. Diabetes causes hepatic and renal ECM turnover. YLE can be useful to partially improve tissue disorders induced by diabetes

Ameliorative Effect of Cactus (Opuntia ficus indica) Extract on Lithium-Induced Nephrocardiotoxicity: A Biochemical and Histopathological Study

Opuntia ficus indica (family Cactaceae) is used in the treatment of a variety of conditions including metal-induced toxicity. The study reports the protective effects of Opuntia ficus indica (CCE) against lithium carbonate-induced toxicity in rats. Nephrocardiotoxicity was induced in male Wistar rats by single dose of lithium carbonate (25 mg/kg b.w twice daily for 30 days). Aqueous extract of Opuntia ficus indica was administered at the dose of 100 mg/kg of b.w by gavage for 60 days. Obtained results revealed that administration of lithium carbonate caused a significant increase in serum creatinine, uric acid, and urea levels. Additionally, a significant decrease in the level of renal and cardiac SOD, CAT, and GPx activities was associated with a significant increase of MDA levels in lithium carbonate group more than those of the control. However, the treatment of experimental rats with CCE prevented these alterations and maintained the antioxidant status. The histopathological observations supported the biochemical evidences of nephrocardioprotection. CCE supplementation could protect against lithium carbonate-induced renal and cardiac injuries in rats, plausibly by the upregulation of antioxidant enzymes and inhibition of MDA to confer the protective effect

Protective effect of cactus cladode extract against cisplatin induced oxidative stress, genotoxicity and apoptosis in balb/c mice: combination with phytochemical composition

Abstract Background Cis-Platinum (II) (cis-diammine dichloroplatinum; CDDP) is a potent antitumor compound widely used for the treatment of many malignancies. An important side-effect of CDDP is nephrotoxicity. The cytotoxic action of this drug is often thought to induce oxidative stress and be associated with its ability to bind DNA to form CDDP–DNA adducts and apoptosis in kidney cells. In this study, the protective effect of cactus cladode extract (CCE) against CDDP-induced oxidative stress and genotoxicity were investigated in mice. We also looked for levels of malondialdehyde (MDA), catalase activity, superoxide dismutase (SOD) activity, chromosome aberrations (CA) test, SOS Chromotest, expressions of p53, bax and bcl2 in kidney and we also analyzed several parameters of renal function markers toxicity such as serum biochemical analysis. Methods Adult, healthy balb/c (20–25 g) male mice aged of 4–5 weeks were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 100 μg/Kg.b.w CDDP. Animals which treated by CDDP and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with CDDP 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with CDDP 3 days a week for 4 weeks. Results Our results showed that CDDP induced significant alterations in all tested oxidative stress markers. In addition it induced CA in bone morrow cells, increased the expression of pro-apoptotic proteins p53 and bax and decreased the expression of anti-apoptotic protein bcl2 in kidney. On the other hand, CDDP significantly increased the levels of urea and creatinine and decreased the levels of albumin and total protein.The treatment of CCE before or after treatment with CDDP showed, (i) a total reduction of CDDP induced oxidative damage for all tested markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations compared to the group treated with CDDP alone (iii) restriction of the effect of CDDP by differential modulation of the expression of p53 which is decreased as well as its associated genes such as bax and bcl2, (iiii) restriction of serums levels of creatinine, urea, albumin and total protein resuming its values towards near normal levels of control. Conclusion We concluded that CCE is beneficial in CDDP-induced kidney dysfunction in mice via its anti-oxidant anti-genotoxic and anti-apoptotic properties against CDDP.</p

Melatonin Improves Endoplasmic Reticulum Stress-Mediated IRE1α Pathway in Zücker Diabetic Fatty Rat

Obesity and diabetes are linked to an increased prevalence of kidney disease. Endoplasmic reticulum stress has recently gained growing importance in the pathogenesis of obesity and diabetes-related kidney disease. Melatonin, is an important anti-obesogenic natural bioactive compound. Previously, our research group showed that the renoprotective effect of melatonin administration was associated with restoring mitochondrial fission/fusion balance and function in a rat model of diabesity-induced kidney injury. This study was carried out to further investigate whether melatonin could suppress renal endoplasmic reticulum (ER) stress response and the downstream unfolded protein response activation under obese and diabetic conditions. Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight (BW)/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Western blot analysis of ER stress-related markers and renal morphology were assessed. Compared to C-ZL rats, higher ER stress response associated with impaired renal morphology was observed in C-ZDF rats. Melatonin supplementation alleviated renal ER stress response in ZDF rats, by decreasing glucose-regulated protein 78 (GRP78), phosphoinositol-requiring enzyme1α (IRE1α), and ATF6 levels but had no effect on phospho-protein kinase RNA-like endoplasmic reticulum kinase (PERK) level. In addition, melatonin supplementation also restrained the ER stress-mediated apoptotic pathway, as indicated by decreased pro-apoptotic proteins phospho-c-jun amino terminal kinase (JNK), Bax, and cleaved caspase-3, as well as by upregulation of B cell lymphoma (Bcl)-2 protein. These improvements were associated with renal structural recovery. Taken together, our findings revealed that melatonin play a renoprotective role, at least in part, by suppressing ER stress and related pro-apoptotic IRE1α/JNK signaling pathway.This work was supported by grant SAF2016-79794-R from the Ministerio de Ciencia e Innovación (Spain) and European Regional Development Fund (ERDF).Ye