scholarly journals Protective role of sildenafil citrate in isoniazid-rifampicin induced histomorphological changes in liver of albino mice

Author(s):  
Najma Hameed ◽  
Khalid Farooq

Objectives: The objective of the study was to reveal the reversal of histo-morphological changes in mice liver induced by combined isoniazid-rifampicin (INH-RIF) therapy with sildenafil treatment. Methods: Twenty-one mice weighing between 25–35 g were enrolled in the study. Randomisation was carried out by simple balloting method. The selected mice were sorted into three groups with 7 mice, each group. In group C (n=7) control group, mice were administered 0.4ml of saline per kg body weight daily intra peritoneally for 21 days. In group R (n=7) INH-RIF group, rifampicin (50 mg/kg) and isoniazid (50 mg/kg), dissolved in 4 ml/kg isotonic saline, were administered intra-peritoneally (ip) daily for 21 days. In group S (n=7) sildenafil administered group, 10 mg/kg sildenafil was given orally by gastric gavage on daily basis along with the intraperitoneal injection of INH-RIF (50 mg/kg each) daily for 21 days. Results: Histopathology revealed hepatotoxicity in group R (INH-RIF), while significant improvement was observed in group C (INH-RIF-sildenafil). Conclusion: Sildenafil citrate possesses hepatoprotective role against INH-RIF induced hepatotoxicity.

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Arash Omidi ◽  
Zahra Totrabi

Different potentially therapeutic approaches to prevent or attenuate gentamicin sulfate (GM) induced nephrotoxicity have been proposed. The present study was conducted to investigate the effect of the saffron petals extracts (<em>Crocus sativus</em>) (SPE) on male Wistar rats with kidney failure. Rats (40) were randomly assigned into five groups of 8 animals each: i) the control group, that received normal saline (0.5 mL/kg); ii) the GM group, that received GM (80 mg/kg) by intraperitoneal (i.p.) injection on a daily basis; iii) the <em>GM+SPE</em> group that received the same dose of GM and SPE (40 mg/kg) by i.p. injection on a daily basis; iv) the <em>GM+2SPE</em> group, that received the same dose of GM and twofold of SPE (80 mg/kg) by i.p. injection on a daily basis; whereas v) <em>2SPE+GM</em> group, that received 80 mg/kg of SPE a week before initiating the treatment with GM (prevention group). Significant differences were seen in the concentration of glucose, blood urea nitrogen (BUN), and creatinine between treatment groups and control in the male Wistar rats. GM was observed to cause nephrotoxicity, which was evidenced by an elevation of serum BUN and creatinine levels. The biochemical findings of the current study are concordant with those of histopathologic findings. The results of this study indicate that SPE especially in dose of 40 mg/kg can ameliorate harmful effects of GM on the kidney. The present results may suggest that the SPE have ameliorative effects on kidney failures induced by GM.


2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.


Author(s):  
Basiru Olaitan Ajiboye ◽  
Babatunji Emmanuel Oyinloye ◽  
Jennifer Chidera Awurum ◽  
Sunday Amos Onikanni ◽  
Adedotun Adefolalu ◽  
...  

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.


2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.


2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 53-57 ◽  
Author(s):  
Devrim Bozkurt ◽  
Selahattin Bicak ◽  
Savas Sipahi ◽  
Huseyin Taskin ◽  
Ender Hur ◽  
...  

Background Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. Objective To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R). Methods 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 – 3 weeks) + peritoneal resting (4 – 6 weeks); C-R group, CG (0 – 3 weeks) + 1 mg/L colchicine (4 – 6 weeks); C-P group, CG (0 – 3 weeks) + 1 mg/L colchicine in drinking water (0 – 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. Result Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. Conclusion We suggest that colchicine may have therapeutic value in the management of EPS.


1977 ◽  
Vol 23 (7) ◽  
pp. 1346-1347 ◽  
Author(s):  
D F Devereux ◽  
C A Michas ◽  
S Rice

Abstract Mongrel dogs were treated intravenously with either 1000 units of beef-lung heparin per kilogram of body weight or with isotonic saline, before intravenous administration of E. coli endotoxin. We found significant differences in circulating norepinephrine concentrations between a heparin-pretreatment group (1.89 +/- 0.39 microgram/liter) and the control group (9.83 +/- 4.64 microgram/liter), but none with respect to epinephrine. Systolic blood pressures at 360 min were also significantly (P less than 0.05) different, 148 +/- 6 mmHg as compared with 118 +/- 13.4 mmHg. Evidently heparin pretreatment can decrease circulating norepinephrine concentrations in the endotoxic state and changes in circulating catecholamine concentrations can affect physiological variables.


2020 ◽  
Vol 21 (12) ◽  
pp. 4348 ◽  
Author(s):  
Ali H. El-Far ◽  
Mohamed A. Lebda ◽  
Ahmed E. Noreldin ◽  
Mustafa S. Atta ◽  
Yaser H. A. Elewa ◽  
...  

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1β, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Zhi-gao Sun ◽  
Ya-zhuo Hu ◽  
Yu-guo Wang ◽  
Jian Feng ◽  
Yong-qi Dou

BuPiHeWei (BPHW) decoction, a classic Traditional Chinese Medicinal (TCM) prescription, has been widely used in clinical practice to relieve digestive symptoms caused by chemotherapy, such as diarrhea and vomiting. The present study aimed to investigate whether BPHW decoction exerted a protective role in the 5-Fu-induced intestinal mucosal injury in the rats by regulating the mechanisms of TLR-4/NF-κB signaling pathway. There were 35 Sprague Dawley rats randomly divided into four groups: normal control group, 5-Fu group, 5-Fu + BPHW decoction group (10.5 g/kg, for five continuous days), and 5-Fu + Bacillus licheniformis capsule group (0.2 g/kg, for five continuous days). Animal models were established by intraperitoneal injection of 5-Fu (30 mg/Kg, for five consecutive days). At the end of the treatment period, body weight, diarrhea score, and histological examination were examined. Furthermore, the expression of TLR-4/NF-κB pathway was detected to reveal its mechanism. The results showed that BPHW decoction effectively reduced diarrhea score and increased body weight and height of villi after 5-Fu chemotherapy. In addition, BPHW decoction could significantly inhibit the expression of TLR-4, NF-κB, and inflammatory factors (including TNF-α, IL-1β, and IL-6) in the intestine, and the efficacy was significantly higher than that of Bacillus licheniformis capsule. In summary, BPHW decoction might be considered an effective drug to alleviate intestinal mucosal injury in the rats induced by 5-Fu.


2012 ◽  
Vol 5 (4) ◽  
pp. 192-200 ◽  
Author(s):  
Vivek Kumar Dwivedi ◽  
Anuj Bhatanagar ◽  
Manu Chaudhary

ABSTRACT We investigated the protective role of ceftriaxone plus sulbactam with VRP1034 (Elores) on hematological, lipid peroxidation, antioxidant enzymatic activities and Cd levels in the blood and tissues of cadmium exposed rats. Twenty-four male rats were divided into three groups of eight rats each. The control group received distilled water whereas group II received CdCl2 (1.5 mg/4 ml/body weight) through gastric gavage for 21 days. Group III received CdCl2 and was treated with ceftriaxone plus sulbactam with VRP1034 for 21 days. The hematological, biochemical, lipid per-oxidation levels and enzymatic parameters were measured in plasma and tissues (brain, liver and kidney) of all groups. The Cd, Zn and Fe levels were measured in blood and tissues of all groups. Our findings showed significantly decreased cadmium (p<0.001), malonaldialdehyde (p<0.001) and myloperoxidase (MPO) levels along with significantly increased hemoglobin (p<0.01), RBC (p<0.05), hematocrit (p<0.05) levels and all antioxidant enzymatic activities (SOD, CAT, GR, GPx) in plasma and tissues of ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. Delta aminolevulinate dehydratase (δ-ALAD) activity was significantly (p<0.001) increased in the blood of ceftriaxone plus sulbactam with VRP1034 treated group as compared with cadmium exposed group. The levels of hepatic and renal parameters were significantly (p<0.001) decreased in ceftriaxone plus sulbactam with VRP1034 treated group as compared to cadmium exposed group. These findings indicate that ceftriaxone plus sulbactam with VRP1034 acts as a potent free radical scavenger and exhibits metal chelating properties that reduce free radical mediated tissue injury and prevent dysfunction of hepatic and renal organs during metal intoxication.


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