Zanthoxylum zanthoxyloides Alkaloidal Extract Improves CCl4-Induced Hepatocellular Carcinoma-Like Phenotypes in Rats

Background. Despite the enrollment of new small molecules such as Sorafenib for the treatment of hepatocellular carcinoma (HCC), HCC still remains a significant contributor to cancer-related mortality and morbidity globally. Zanthoxylum zanthoxyloides is long suspected of possessing anticancer bioactive compounds that may hold the prospect of adjunctive therapy against inflammation-related cancers such as HCC. Objective. This study assessed the effects of an alkaloidal extract of the leaves of Zanthoxylum zanthoxyloides on CCl4/olive oil (1 : 1 v/v)-induced HCC-like phenotypes in rats. Materials and Methods. Zanthoxylum zanthoxyloides alkaloidal extract (ZZAE) was prepared using Soxhlet and liquid-liquid extraction methods. Subsequently, ZZAE was characterized phytochemically. In the curative method, experimental HCC was established in adult (8–10 weeks old) male Sprague-Dawley rats weighing 150–300 g by twice-daily administration of CCl4/olive oil (1 : 1 v/v) (2 mL/kg ip). After confirmation of experimental HCC in rats, the rats were randomly reassigned into seven (7) groups of seven (7) rats each and treated daily for 12 weeks as follows: control (normal saline, 5 ml/kg po), model (CCl4, 5 ml/kg, ip), ZZAE (50, 100, and 200 mg/kg po), carvedilol (6.25 mg/kg po), and 20% Tween20 (1 mL/rat, po). To assess whether ZZAE has a prophylactic (preventive) effect, rats were first treated with ZZAE and later exposed to CCl4 reconstituted in olive oil. Results. ZZAE (100 and 200 mg/kg) and carvedilol decreased tumor incidence compared to that of control. Compared to control, ZZAE (100 and 200 mg/kg) significantly ( P < 0.05 ) improved serum GGT. Compared to control, ZZAE improved hepatohistological distortions induced by CCl4/olive oil and also improved liver/body weight ratio. Compared to water, ZZAE arrested mitosis in the Allium cepa assay. Conclusion. ZZAE ameliorated CCl4/olive oil-induced HCC-like phenotype in rats and demonstrated general hepatoprotective effects by improving liver and kidney function markers. This finding rationalizes the need for further studies on ZZAE as a potential source of bioactive anti-HCC compounds.

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Comparative Biochemical and Histopathological Studies on the Efficacy of Metformin and Virgin Olive Oil against Streptozotocin-Induced Diabetes in Sprague-Dawley Rats

Journal of Diabetes Research ◽

10.1155/2018/4692197 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Khadijah Saeed Balamash ◽

Huda Mohammed Alkreathy ◽

Elham Hamed Al Gahdali ◽

Sawsan Omer Khoja ◽

Aftab Ahmad

Keyword(s):

Olive Oil ◽

Virgin Olive Oil ◽

Inflammatory Cells ◽

Extra Virgin Olive Oil ◽

Diabetic Control ◽

Diabetic Rats ◽

Diabetic Patients ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Liver And Kidney

Treatment of diabetic patients with antioxidant, such as extra virgin olive oil (EVOO), may be beneficial in numerous debilitating complexities. This study was aimed at assessing the protective role of virgin olive oil in reducing hyperglycemia in streptozotocin- (STZ-) induced diabetic rats. Thirty-six healthy male Sprague-Dawley rats were divided into six groups (6 rats per group) including nondiabetic control (NC), diabetic control (DC), and animals treated with metformin, olive oil, and a combination of olive oil and metformin, respectively. The protective effect of olive oil was evaluated by determining the biochemical parameters (lipid profile, liver, and kidney) and by studying the histopathological alterations in pancreas, liver, and kidney tissues. The results showed a significant increase in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels in diabetic rats. ALP levels remained significantly elevated in the diabetic rats that were treated with metformin and/or olive oil, and the highest level was noted in the group treated with olive oil (568.33 U/L). Contrarily, pretreatment with olive oil significantly decreased ALT (67.64 U/L) and ALP (226.17 U/L) levels. Histopathological data revealed that all the disorganized islets of Langerhans along with the clusters of inflammatory cells were absent in the group pretreated with the combination of virgin olive oil and metformin, which shows that prophylactic administration of this combination reduces the diabetic complications in a much better way. Therefore, pretreatment with olive oil with or without metformin is an encouraging approach for diabetes therapy with immense potential.

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Isoelectric focusing of glutathione S-transferases from rat liver and kidney

Biochemical Journal ◽

10.1042/bj1750937 ◽

1978 ◽

Vol 175 (3) ◽

pp. 937-943 ◽

Cited By ~ 28

Author(s):

Barbara F. Hales ◽

Valerie Jaeger ◽

Allen H. Neims

Keyword(s):

Substrate Specificity ◽

Isoelectric Focusing ◽

Transferase Activity ◽

Sprague Dawley ◽

Substrate Specificities ◽

Liver Cytosol ◽

Sprague Dawley Rats ◽

Isoelectric Points ◽

Liver And Kidney ◽

Glutathione S Transferases

The glutathione S-transferases that were purified to homogeneity from liver cytosol have overlapping but distinct substrate specificities and different isoelectric points. This report explores the possibility of using preparative electrofocusing to compare the composition of the transferases in liver and kidney cytosol. Hepatic cytosol from adult male Sprague–Dawley rats was resolved by isoelectric focusing on Sephadex columns into five peaks of transferase activity, each with characteristic substrate specificity. The first four peaks of transferase activity (in order of decreasing basicity) are identified as transferases AA, B, A and C respectively, on the basis of substrate specificity, but the fifth peak (pI6.6) does not correspond to a previously described transferase. Isoelectric focusing of renal cytosol resolves only three major peaks of transferase activity, each with narrow substrate specificity. In the kidney, peak 1 (pI9.0) has most of the activity toward 1-chloro-2,4-dinitrobenzene, peak 2 (pI8.5) toward p-nitrobenzyl chloride, and peak 3 (pI7.0) toward trans-4-phenylbut-3-en-2-one. Renal transferase peak 1 (pI9.0) appears to correspond to transferase B on the basis of pI, substrate specificity and antigenicity. Kidney transferase peaks 2 (pI8.5) and 3 (pI7.0) do not correspond to previously described glutathione S-transferases, although kidney transferase peak 3 is similar to the transferase peak 5 from focused hepatic cytosol. Transferases A and C were not found in kidney cytosol, and transferase AA was detected in only one out of six replicates. Thus it is important to recognize the contribution of individual transferases to total transferase activity in that each transferase may be regulated independently.

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Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽

10.1161/hyp.36.suppl_1.723-a ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 723-723

Author(s):

Qing-Feng Tao ◽

Diego Martinez vasquez ◽

Ricardo Rocha ◽

Gordon H Williams ◽

Gail K Adler

Keyword(s):

Myocardial Infarction ◽

Drinking Water ◽

Mineralocorticoid Receptor ◽

Critical Role ◽

Weight Ratio ◽

Myocardial Necrosis ◽

Receptor Activation ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

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Abstract 114: K+ Rich Diet During Angiotensin II Hypertension Reduces Renal Na-Cl Cotransporter and Phosphorylation, but Not Blood Pressure

Hypertension ◽

10.1161/hyp.66.suppl_1.114 ◽

2015 ◽

Vol 66 (suppl_1) ◽

Author(s):

Luciana C Veiras ◽

Jiyang Han ◽

Donna L Ralph ◽

Alicia A McDonough

Keyword(s):

Blood Pressure ◽

Urine Volume ◽

Weight Ratio ◽

Distal Tubule ◽

Reduce Blood Pressure ◽

Ang Ii ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

K Secretion ◽

Pressure Natriuresis

During Ang II hypertension distal tubule Na-Cl Cotransporter (NCC) abundance and its activating phosphorylation (NCCp), as well as Epithelial Na+ channels (ENaC) abundance and activating cleavage are increased 1.5-3 fold. Fasting plasma [K+] is significantly lower in Ang II hypertension (3.3 ± 0.1 mM) versus controls (4.0 ± 0.1 mM), likely secondary to ENaC stimulation driving K+ secretion. The aim of this study was to test the hypothesis that doubling dietary K+ intake during Ang II infusion will lower NCC and NCCp abundance to increase Na+ delivery to ENaC to drive K+ excretion and reduce blood pressure. Methods: Male Sprague Dawley rats (225-250 g; n= 7-9/group) were treated over 2 weeks: 1) Control 1% K diet fed (C1K); 2) Ang II infused (400 ng/kg/min) 1% K diet fed (A1K); or 3) Ang II infused 2% K diet fed (A2K). Blood pressure (BP) was determined by tail cuff, electrolytes by flame photometry and transporters’ abundance by immunoblot of cortical homogenates. Results: As previously reported, Ang II infusion increased systolic BP (from 132 ± 5 to 197 ± 4 mmHg), urine volume (UV, 2.4 fold), urine Na+ (UNaV, 1.3 fold), heart /body weight ratio (1.23 fold) and clearance of endogenous Li+ (CLi, measures fluid volume leaving the proximal tubule, from 0.26 ± 0.02 to 0.51 ± 0.01 ml/min/kg) all evidence for pressure natriuresis. A2K rats exhibited normal plasma [K+] (4.6 ± 0.1 mM, unfasted), doubled urine K+ (UKV, from 0.20 to 0.44 mmol/hr), and increased CLi (to 0.8 ± 0.1 ml/min/kg) but UV, UNaV, cardiac hypertrophy and BP were unchanged versus the A1K group. As expected, NCC, NCCpS71 and NCCpT53 abundance increased in the A1K group to 1.5 ± 0.1, 2.9 ± 0.5 and 2.8 ± 0.4 fold versus C1K, respectively. As predicted by our hypothesis, when dietary K+ was doubled (A2K), Ang II infusion did not activate NCC, NCCpS71 nor NCCpT53 (0.91 ± 0.04, 1.3 ± 0.1 and 1.6 ± 0.2 fold versus C1K, respectively). ENaC subunit abundance and cleavage increased 1.5 to 3 fold in both A1K and A2K groups; ROMK was unaffected by Ang II or dietary K. In conclusion, evidence is presented that stimulation of NCC during Ang II hypertension is secondary to K+ deficiency driven by ENaC stimulation since doubling dietary K+ prevents the activation. The results also indicate that elevation in BP is independent of NCC activation

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Naringin, a natural flavonone glycoside attenuates N-nitrosodiethylamine- induced hepatocellular carcinoma in sprague-dawley rats

Pharmacognosy Magazine ◽

10.4103/pm.pm_94_21 ◽

2021 ◽

Vol 17 (6) ◽

pp. 196

Author(s):

ShaktiPrasad Pattanayak ◽

Reetuparna Acharya ◽

Namita Mishra ◽

Abhishek Kumar ◽

Pritha Bose ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Cinnamomum cassia ameliorates Ni-NPs-induced liver and kidney damage in male Sprague Dawley rats

Human & Experimental Toxicology ◽

10.1177/0960327120930125 ◽

2020 ◽

Vol 39 (11) ◽

pp. 1565-1581

Author(s):

S Iqbal ◽

F Jabeen ◽

C Peng ◽

MU Ijaz ◽

AS Chaudhry

Keyword(s):

Dependent Manner ◽

Sprague Dawley ◽

Cinnamomum Cassia ◽

Preliminary Information ◽

Sprague Dawley Rats ◽

Liver And Kidney ◽

Altered Blood ◽

Biochemical Analyses ◽

Dose Dependent ◽

Different Doses

Nickel nanoparticles (Ni-NPs) have been widely used in various industries related to electronics, ceramics, textiles, and nanomedicine. Ambient and occupational exposure to Ni-NPs may bring about potential detrimental effects on animals and humans. Thus, there is a growing effort to identify compounds that can ameliorate NPs-associated pathophysiologies. The present study examined Cinnamomum cassia ( C. cassia) bark extracts (CMBE) for its ameliorative activity against Ni-NPs-induced pathophysiological and histopathological alterations in male Sprague Dawley rats. The biochemical analyses revealed that dosing rats with Ni-NPs at 10 mg/kg/body weight (b.w.) significantly altered the normal structural and biochemical adaptations in the liver and kidney. Conversely, supplementations with CMBE at different doses (225, 200, and 175 mg/kg/b.w. of rat) ameliorated the altered blood biochemistry and reduced the biomarkers of liver and kidney function considerably ( p < 0.05) in a dose-dependent manner. However, the best results were at 225 mg/kg/b.w. of rat. The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated liver and kidney damages. Future investigations are needed to explore C. cassia mechanism of action and isolation of single constituents of C. cassia to assess their pharmaceutical importance accordingly.

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Arum conophalloides Aqueous Extract Induced Hepatotoxicity in Rat; Histopathological, Biochemical, and mir-122 Assessments

MicroRNA ◽

10.2174/2211536608666191016142400 ◽

2020 ◽

Vol 9 (3) ◽

pp. 224-231

Author(s):

Amin Derakhshanfar ◽

Javad Moayedi ◽

Mahjoob Vahedi ◽

Abouzar Valizadeh

Keyword(s):

Aqueous Extract ◽

Fold Increase ◽

Normal Structure ◽

Serum Levels ◽

Sprague Dawley ◽

Hydroalcoholic Extract ◽

Sprague Dawley Rats ◽

Liver And Kidney ◽

Biochemical Indices ◽

Potential Hepatotoxicity

Background: Arum conophalloides (A. conophalloides) is a wild edible delicate plant, widely used in traditional medicine. Objective: This study aimed to examine the effects of A. conophalloides extracts on biochemical, molecular, and histopathological changes in the rat. Methods: Fifty adult male Sprague-Dawley rats were divided into 5 groups (10 each) as follows: G1 or control, received distilled water; G2 and G3, treated with the aqueous extract at doses of 200 and 400 mg/kg; G4 and G5, treated with the hydroalcoholic extract at doses of 200 and 400 mg/kg. Prior to and at the end of the experiments, the serum levels of biochemistry parameters and the relative expression of miR-122 were assessed. Moreover, the liver and kidney tissues were examined microscopically. Results: Liver and kidney tissues showed normal structure in all groups. There were no significant changes in biochemical indices or the expression of miR-122 in the extract-treated groups at the dose of 200 mg/kg. However, the group that received the aqueous extract at the dose of 400 mg/kg exhibited a significantly lower level of HDL, LDL, ALT, and ALP in comparison to the control. Additionally, miR-122 expression in this group exhibited a 10-fold increase (P=0.009). Conclusion: The serum level of hepatocyte-specific miR-122 will be more helpful in detecting hepatic changes in early stages than ALT and AST activity or histopathological evaluations of liver sections. Our findings highlight the potential hepatotoxicity of A. conophalloides aqueous extract in a rat model.

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Toxicological Features ofCatha edulis(Khat) on Livers and Kidneys of Male and Female Sprague-Dawley Rats: A Subchronic Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/829401 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Abdulsamad Alsalahi ◽

Mahmood Ameen Abdulla ◽

Mohammed Al-Mamary ◽

Mohamed Ibrahim Noordin ◽

Siddig Ibrahim Abdelwahab ◽

...

Keyword(s):

Male Rats ◽

High Dose ◽

Sprague Dawley ◽

Catha Edulis ◽

Male And Female ◽

Sd Rats ◽

Sprague Dawley Rats ◽

Serum Aspartate Aminotransferase ◽

Liver And Kidney ◽

Kg Medium

Hepato- and nephrotoxicity of Khat consumption (Catha edulisForskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120 g) were distributed randomly into four groups of males and female (n=12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract ofCatha edulisorally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.

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Effect of urinary alkalinisation and acidification on the tissue distribution of hexachlorophene in rats

Human & Experimental Toxicology ◽

10.1177/096032719501401003 ◽

1995 ◽

Vol 14 (10) ◽

pp. 795-800 ◽

Cited By ~ 2

Author(s):

RJ Flanagan ◽

M. Ruprah ◽

AV Strutt ◽

P. Malarkey ◽

A. Cockburn

Keyword(s):

Oxidative Phosphorylation ◽

Sodium Bicarbonate ◽

Tissue Distribution ◽

Ammonium Chloride ◽

Acute Poisoning ◽

Sprague Dawley ◽

Urine Ph ◽

Sprague Dawley Rats ◽

Median Plasma ◽

Liver And Kidney

1 Urinary alkalinisation may be helpful in treating acute poisoning with uncouplers of oxidative phosphorylation containing a phenolic hydroxyl (pKa 4-6) or other acidic moiety. 2 We studied the effects of urine alkalinisation and acidi fication on the tissue distribution of hexachlorophene (HCP, pKa 5.7) in male Sprague Dawley rats (10 rats/group). 3 Ammonium chloride (10 mL kg-1, 2% m/v) or sodium bicarbonate (10 mL kg-1, 2% m/v) were administered by gavage on three occasions over 24 h, prior to a single gavage dose of HCP (180 mg kg-1). Controls received aqueous sodium chloride (10 mL kg-1, 0.9% m/v) fol lowed by either HCP (180 mg kg-1) or vehicle alone. 4 Urine pH, body mass and body temperature were moni tored during the study and, at the conclusion of the experiment (12 h post-HCP dose), organ mass (liver, kidney, brain), and plasma, urine and tissue HCP concentrations were measured. 5 No clinical features of toxicity were observed in any group. However, sodium bicarbonate significantly reduced median HCP in liver — median plasma and kidney HCP concentrations were also reduced but not significantly. Conversely, ammonium chloride signifi cantly increased median HCP concentrations in liver and kidney — median plasma HCP was also increased but not significantly. 6 The results provide some support for the hypothesis that blood pH influences the tissue distribution of uncou plers of oxidative phosphorylation containing an acidic moiety. Urinary alkalinisation may be useful in treating acute poisoning with these compounds.

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Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats

Open Medicine ◽

10.2478/s11536-009-0021-x ◽

2009 ◽

Vol 4 (2) ◽

pp. 184-191 ◽

Cited By ~ 8

Author(s):

Kerim Cayir ◽

Ali Karadeniz ◽

Abdulkadir Yildirim ◽

Yildiray Kalkan ◽

Akar Karakoc ◽

...

Keyword(s):

Lipid Peroxidation ◽

Therapeutic Potential ◽

Protective Effects ◽

Sprague Dawley ◽

Glutathione S Transferase ◽

Kidney Dysfunction ◽

Degree Of Protection ◽

Sprague Dawley Rats ◽

Liver And Kidney ◽

Endogenous Antioxidants

AbstractThe present study was designed to investigate the protective effects of L-carnitine (LC) on changes in the levels of lipid peroxidation and endogenous antioxidants induced by cisplatin (cis-diamminedichloroplatinum II, CDDP) in the liver and kidney tissues of rats. Twenty-four Sprague Dawley rats were equally divided into four groups of six rats each: control, cisplatin, L-carnitine, and L-carnitine plus cisplatin. The degree of protection produced by L-carnitine was evaluated by determining the level of malondialdehyde (MDA). The activity of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), and superoxide dismutase (SOD) were estimated from liver and kidney homogenates, and the liver and kidney were histologically examined as well. L-carnitine elicited significant liver and kidney protective activity by decreasing the level of lipid peroxidation (MDA) and elevating the activity of GSH, GSHPx, GST, and SOD. Furthermore, these biochemical observations were supported by histological findings. In conclusion, the present study indicates a significant role for reactive oxygen species (ROS) and their relation to liver and kidney dysfunction, and points to the therapeutic potential of LC in CDDP-induced liver and kidney toxicity.

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