Protective Effect of Calcium Dobesilate Administration Against Hepatorenal Damage Induced By CCL4 In Male Mice

Author(s):  
Elham Hakimizadeh ◽  
Ayat Kaeidi ◽  
Mohammadreza Rahmani ◽  
Mohammad Allahtavakoli ◽  
Jalal Hassanshahi

Abstract Purpose: Calcium dobesilate (CaD) has antioxidant and anti-inflammatory properties. In this study, the protective effects of CaD against hepatorenal damage induced by CCL4 in male mice were evaluated. Methods: Thirty male mice randomly were divided into five groups: Control, CaD 100 mg/kg, CCL4, CCL4+CaD 50 mg/kg, and CCL4+CaD 100 mg/kg. Drugs were administered orally once a day for 4-weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase and aspartate aminotransferase levels) were determined. Also, hepatic and renal tissue oxidant/antioxidant markers (glutathione peroxidase, malondialdehyde, total antioxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, and Bcl-2 protein levels were measured by immunoblotting method. The liver and kidney histopathological changes were evaluated by H&E staining.Results: CCL4 induces significant oxidative stress in the kidney and liver that was concomitant with functional and histopathological abnormalities in these organs in the CCL4 group versus the control (P<0.05). CaD could significantly improve the histopathological change in the liver and kidney tissues of CCL4+CaD 100 mg/kg mice versus the CCL4 group (P<0.05). In addition, CaD attenuated apoptosis in the liver and kidney tissues (P<0.05).Conclusion: The protective effect of CaD may be related to its anti-inflammatory and antioxidant properties.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Chao Liu ◽  
Yung-Fong Tsai ◽  
Hsin-I Tsai ◽  
Huang-Ping Yu

Resveratrol, a natural polyphenolic compound of grape and red wine, owns potential anti-inflammatory effects, which results in the reduction of cytokines overproduction, the inhibition of neutrophil activity, and the alteration of adhesion molecules expression. Resveratrol also possesses antioxidant, anti-coagulation and anti-aging properties, and it may control of cell cycle and apoptosis. Resveratrol has been shown to reduce organ damage following traumatic and shock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the activation of estrogen receptor, the regulation of the sirtuin 1/nuclear factor-kappa B and mitogen-activated protein kinases/hemeoxygenase-1 pathway, and the mediation of proinflammatory cytokines and reactive oxygen species formation and reaction. In the recent studies, resveratrol attenuates hepatocyte injury and improves cardiac contractility due to reduction of proinflammatory mediator expression and ameliorates hypoxia-induced liver and kidney mitochondrial dysfunction following trauma and hemorrhagic injuries. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to protect organ function in trauma-hemorrhagic injury. In this review, the organ-protective and anti-inflammatory effects of resveratrol in trauma-hemorrhagic injury will be discussed.


2012 ◽  
Vol 2 (10) ◽  
pp. 351
Author(s):  
Fu-Chao Liu ◽  
Huang-Ping Yu

Resveratrol, is a polyphenol that can be extracted from grapes and red wine, possess potential anti-inflammatory effects, which would result in the reduction of cytokine production, the alteration of the expression of adhesion molecule molecules, and the inhibition of neutrophil function. Resveratrol might also act as an antioxidant, anti-aging, and control of cell cycle and apoptosis. Resveratrol has been shown to have protective effects for patients in shock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the regulation of the mitogen-activated protein kinases (MAPK)/ hemeoxygenase-1 (HO-1) pathway, activates estrogen receptor (ER), and the mediation of pro-inflammatory cytokines, reactive oxygen species (ROS) formation and reactive. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to maintain organ function following trauma-hemorrhage.Key words: resveratrol, anti-inflammatory, trauma-hemorrhage.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hsin-Hsueh Shen ◽  
Yu-Shiuan Tseng ◽  
Ni-Chun Kuo ◽  
Ching-Wen Kung ◽  
Sherif Amin ◽  
...  

Heat stroke (HS) is a life-threatening illness and defined as when body temperature elevates above 40°C accompanied by the systemic inflammatory response syndrome that results in multiple organ dysfunctions. α-Lipoic acid (ALA) acts as a cofactor of mitochondrial enzymes and exerts anti-inflammatory and antioxidant properties in a variety of diseases. This study investigates the beneficial effects of ALA on myocardial injury and organ damage caused by experimental HS and further explores its underlying mechanism. Male Wistar rats were exposed to 42°C until their rectal core temperature reached 42.9°C and ALA was pretreared 40 or 80 mg/kg (i.v.) 1.5 h prior to heat exposure. Results showed that HS-induced lethality and hypothermia were significantly alleviated by ALA treatment that also improved plasma levels of CRE, LDH, and CPK and myocardial injury biomarkers myoglobin and troponin. In addition, ALA reduced cardiac superoxide anion formation and protein expression of cleaved caspase 3 caused by HS. Proinflammatory cytokine TNF-α and NF-κB pathways were significantly reduced by ALA treatment which may be associated with the upregulation of Hsp70. ALA significantly increased the Atg5-12 complex and LC3B II/LC3B I ratio, whereas the p62 and p-mTOR expression was attenuated in HS rats, indicating the activation of autophagy by ALA. In conclusion, ALA ameliorated the deleterious effects of HS by exerting antioxidative and anti-inflammatory capacities. Induction of Hsp70 and activation of autophagy contribute to the protective effects of ALA in HS-induced myocardial injury.


2019 ◽  
Vol 317 (2) ◽  
pp. G90-G97 ◽  
Author(s):  
Doug N. Halligan ◽  
Mohammed N. Khan ◽  
Eric Brown ◽  
Catherine R. Rowan ◽  
Ivan S. Coulter ◽  
...  

Inflammatory bowel disease (IBD) is characterized by epithelial barrier dysfunction with resultant inflammation as the mucosal immune system becomes exposed to luminal antigens. The hydroxylase inhibitor dimethyloxalylglycine (DMOG) reduces symptoms in experimental colitis through the upregulation of genes promoting barrier function and inhibition of epithelial cell apoptosis. The immunosuppressive drug cyclosporine reduces inflammation associated with IBD via suppression of immune cell activation. Given the distinct barrier protective effect of DMOG and the anti-inflammatory properties of cyclosporine, we hypothesized that combining these drugs may provide an enhanced protective effect by targeting both barrier dysfunction and inflammation simultaneously. We used the dextran sulfate sodium model of colitis in C57BL/6 mice to determine the combinatorial efficacy of cyclosporine and DMOG. While cyclosporine and DMOG ameliorated disease progression, in combination they had an additive protective effect that surpassed the level of protection afforded by either drug alone. The ability of DMOG to augment the anti-inflammatory effects of cyclosporine was largely due to preservation of barrier function and at least in part due to zonula occludens-1 regulation. We propose that combining the barrier protective effects of a hydroxylase inhibitor with the anti-inflammatory effects of cyclosporine provides added therapeutic benefit in colitis. NEW & NOTEWORTHY Inflammatory bowel disease is the result of decreased intestinal epithelial barrier function leading to exposure of the mucosal immune system to luminal antigens causing inflammation, which in turn further decreases epithelial barrier function. We demonstrate for the first time that strengthening the epithelial barrier with a hydroxylase inhibitor in combination with the administration of the immunosuppressive cyclosporine provides additive therapeutic advantage in a murine model of colitis


Author(s):  
Siva Reddy Challa ◽  
Veena Gadicherla ◽  
Mandava V. Basaveswara Rao ◽  
P. Ramakrishna ◽  
K.Pavan Kumar

The study was aimed to evaluate the protective effects of alcoholic extracts of Strawberry and Blueberry fruits [AESF and AEBF] in acute pancreatitis in rats. Treatment groups received AESF and AEBF at doses of 200 and 400 mg/kg for 7 days with prior injections of L-arginine on 5th day. Biochemical parameters were estimated in serum and pancreatic tissue samples. Histopathological studies and DNA fragmentation assay were carried out in isolated pancreatic tissue. The results of the study indicated that treatment of AESF and AEBF exhibited a significant dose dependent protective effect. Upon the treatment, anti-oxidant enzymes were significantly (*pless than 0.05) increased. Biochemical results were correlated with the histopathological findings. In addition, the DNA fragmentation assay showed an intact DNA in pancreatic cells of treated groups. In conclusion, berry fruit extracts exerted a potential protective effect against L-arginine induced damage in rat pancreas, at least in part, due to its antioxidant properties.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Noha A. El-Boghdady ◽  
Nourtan F. Abdeltawab ◽  
Mohammed M. Nooh

Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity is attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK) have anti-inflammatory and antioxidant properties. The protective effects of Res, MK, or their combination against PQ-induced acute liver injury have not been investigated before. Therefore, we explored the protective potential of Res and/or MK against PQ hepatic toxicity in a mouse model. Mice were randomly assigned to five groups: group I served as the normal control and group II received a single dose of PQ (50 mg/kg, i.p.). Groups III, IV, and V received PQ plus oral Res (5 mg/kg/day), MK (10 mg/kg/day), and Res/MK combination, respectively. Res and/or MK reduced PQ-induced liver injury, evidenced by normalization of serum total protein, ALT, and AST. Res and/or MK significantly reversed PQ-induced oxidative stress markers glutathione and malondialdehyde. Res and/or MK significantly reduced PQ-induced inflammation reflected in TNF-α levels. Furthermore, Res and/or MK reversed PQ-induced apoptosis assessed by differential expression of p53, Bax, and Bcl-2. Histopathologic examination supported the biochemical findings. Although Res and MK displayed antioxidative, anti-inflammatory, and antiapoptotic activities, their combination was not always synergistic.


Author(s):  
B. A. Mba ◽  
C. S. Alisi ◽  
A. C. Ene

Aim: The aim of this study is to evaluate the antioxidant properties and protective effects of aqueous anti-ulcer drug (AQAUD) against aspirin-induced gastric ulcer in albino rats. Methods: In this study, 30 male albino rats were divided into 5 groups of 6 each. Rats in group I served as normal control and received food and water. Animals in group II received food and water in addition to aspirin (400 mg/kg.b.wt) orally on the 14th day. Rats in groups III, IV and V received “AQAUD” (250 mg/kg.b.wt), (500 mg/kg.b.wt) and Omeprazole (20 mg/kg.b.wt) respectively for 14 days and aspirin (400 mg/kg.b.wt) orally on the 14th day. In vitro antioxidant property of “AQAUD” was assessed by its nitric oxide and hydroxyl radicals scavenging properties. The ulcer protective effect of “AQAUD” was assessed by determining the free and total acidity, ulcer index and % protection in the stomach content. The antioxidant potential in animals was evaluated by determining the concentrations of malondialdehyde and reduced glutathione. Superoxide dismutase and catalase activities were assayed in the stomach homogenates to further assess antioxidant potential. Total phenolics and flavonoid compounds were quantified to know the antioxidant content. Histopathological assessment of the gastric mucosa was used to assess the protective potentials of “AQAUD”. Data were analyzed using Statistical Package for Social Science (SPSS) version 21. Results: The results revealed that free acidity and ulcer indexes were significantly (p<0.05) reduced by “AQAUD”. There was a significant decrease in SOD activity of the stomach homogenates when compared to the aspirin group, with values for “AQAUD” 250 mg/kg.b.wt and “AQAUD” 500 mg/kg b.wt as 37.24±5.39ux10-2/mg protein and 23.64±2.91ux10-2/mg protein respectively. Result of acute toxicity testing showed that “AQAUD” is generally safe up to 5000 mg/kg b.wt. Conclusion: The results revealed that treatment with aspirin caused loss of gland architecture with erosion of epithelial layer, but AQAUD treatment ameliorated the effect of aspirin administration. The study revealed that “AQAUD” has considerable antioxidant potentials and can effectively protect against gastric ulcers.


2020 ◽  
Vol 10 ◽  
Author(s):  
Valéria Dornelles Gindri Sinhorin ◽  
Naiéle Sartori Patias ◽  
Fernando Rafael de Moura ◽  
Ana Paula Simões da Cunha ◽  
Ritane Rose da Silva Lima ◽  
...  

Background: Protium heptaphyllum (Aubl.) March resin is accepted as an analgesic, healing, expectorant, anti-inflammatory, antinociceptive and gastroprotective. However, there are no specific studies with leaves of this plant. Objective: This study identified the chemical composition and biological activity of crude ethanolic extract (EE) and ethyl acetate (EA) fraction from P. heptaphyllum. Methods: Mice were intoxicated with acetaminophen (PCM; 250 mg/kg), subsequently treated with EE and EA (100 mg/kg) for 7 days via gavage. Plasma analyzes and liver and kidney homogenates of the animals were performed. Results: The extract and fraction showed the presence of phenols and flavonoids. Three main flavonoids were identified by HPLC-UV, LC-MS/MS fractionation, quercetin-3-β-D-glycoside, myricetin and quercetin. For total antioxidant potential tests, EE presented EC50 of 75 μg/mL and 100 μg/mL for EA. ALT, AST and ALP enzymes activity increased in the PCM-exposed plasma, but EA decreased these activities at control levels for ALT and AST. Animal glycemic levels decreased with EE and EA, which may be due to a possible hypoglycemic effect of the plant. In liver tissue, SOD was unchanged, CAT, GSH and ASA decreased in the PCM group, but EA was able to reverse these effects. TBARS and PC were reduced by both treatments. In renal tissue, EA fraction recovered GST activity, GSH levels were restored by EE and EA and PC was reduced by treatments. Conclusion: This antioxidant effect may be due to the presence of the flavonoids identified which are already well known for their antioxidant properties.


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