Diosmin exerts hepatoprotective and antihyperglycemic effects against sodium arsenite-induced toxicity through the modulation of oxidative stress and inflammation in mice

BackgroundChronic exposure to high concentrations of inorganic arsenic (NaAsO₂) in drinking water is related to an increase in the risk of liver toxicity and diabetes. Diosmin has various pharmacological properties, including antioxidant and anti-inflammatory properties. This study was designed to investigate the protective effects of diosmin on diabetes and hepatotoxicity caused by NaAsO₂.MethodsSixty male 8-week-old NMRI mice, weighing 25 ± 2 g, were randomly selected and put into six groups. The control (Group 1) was treated orally with distilled water, group 2 was treated with diosmin (100 mg/kg, p.o), group 3 received NaAsO₂ (10 mg/kg, p.o), and groups 4, 5, 6 received diosmin (25, 50, 100 mg/kg, p.o), respectively and NaAsO₂ (10 mg/kg, p.o). After 29 days, fasting blood sugar (FBS) measurement and glucose tolerance test were done. The mice were sacrificed on day 31, and blood and tissue (liver and pancreas) samples were taken. Then, serum and tissue samples were studied for biochemical and histological evaluations.ResultsThe results demonstrated that diosmin ameliorated glucose intolerance and decreased FBS compared to the NaAsO₂ group. Diosmin (50 and 100 mg/kg) improved the serum factors of liver function (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) in the groups receiving NaAsO₂. Moreover, increased levels of nitric oxide, tumor necrosis factor-alpha, and thiobarbituric acid reactive substances in liver tissue induced by NaAsO₂ were diminished by diosmin treatment. Administration of diosmin increased total thiol and enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase in liver tissue. Furthermore, treatment with diosmin reduced the increase in protein amount of Sirtuin 3 and nuclear factor kappa B in the groups receiving NaAsO₂. Also, the liver and pancreas histological lesions induced by NaAsO₂ were attenuated by diosmin treatment.ConclusionDiosmin has a preventive effect against hepatotoxicity and diabetes induced by NaAsO₂ in mice through its antioxidant and anti-inflammatory properties.     

Lucrative antioxidant effect of metformin against cyclophosphamide induced nephrotoxicity

Cyclophosphamide is anticancer drug with a well-Known nephrotoxicity. This work was applied to study the lucrative antioxidant influence of metformin as co-therapy on the nephrotoxicity induced by cyclophosphamide in the treatment of different cancer diseases. Four groups of male Sprague Dawley rats were used; Control group (C) received single I.P. injection of 0.2 ml saline, Metformin (MET) group received daily gavage of 200 mg/kg metformin for two weeks, Cyclophosphamide (CP) group received single I.P. injection of 200 mg/kg CP, Protector group (CP.MET) received daily gavage of 200 mg/kg metformin for two weeks and single I.P. injection of 200 mg/kg CP at day 7. By day 14 rats were euthanized. Samples were collected from kidney tissues and blood for kidney function evaluation, histopathological and assessment of oxidative stress markers. The results disclosed that CP yields many functional and structural damage to the kidney, worsened oxidative stress markers and kidney function indicators. The protector group displayed better kidney tissue morphology, acceptable kidney function indicators as well as satisfactory oxidative stress markers.In assumption, metformin could be combined with CP owing to its lucrative effect counter to CP persuaded nephrotoxicity.     

Doxorubicin-induced alterations in kidney functioning,oxidative stress,DNA damage,and renal tissue morphology; Improvement by Acacia hydaspica tannin-rich ethyl acetate fraction

Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with toxic effects. We examined the nephroprotective potential of A. hydaspica polyphenol-rich ethyl acetate extract (AHE) against DOX persuaded nephrotoxicity. 36 male Sprague Dawley rats were randomly assorted into 6 groups. Control group received saline; DOX group: 3 mg/kg b.w. dosage of DOX intraperitoneally for 6 weeks (single dose/week). In co-treatment groups, 200 and 400 mg/kg b.w AHE was given orally for 6 weeks in concomitant with DOX (3 mg/kg b.w, i.p. injection per week) respectively. Standard group received silymarin 400 mg/kg b.w daily + DOX (single dose/week). Biochemical kidney function tests, oxidative stress markers, genotoxicity, antioxidant enzyme status, and histopathological changes were examined. DOX caused significant body weight loss and decrease kidney weight. DOX-induced marked deterioration in renal function indicators in both urine and serum, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin, blood urea nitrogen, etc. Also, DOX treatment increases renal tissue oxidative stress markers, while lower antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. AHE co-treatment ameliorates DOX-prompted changes in serum and urine chemistry. Likewise, AHE treatment decreases sensitive markers of oxidative stress and prevented DNA damages by enhancing antioxidant enzyme levels. DOX induction in rats also caused DNA fragmentation which was restored by AHE co-treatment. Moreover, the histological observations evidenced that AHE effectively rescued the kidney tissue from DOX interceded oxidative damage. Our results suggest that co-treatment of AHE markedly improve DOX-induced deleterious effects in a dose-dependent manner. The potency of AHE co-treatment at 400 mg/kg dose is similar to silymarin. These outcomes revealed that A. hydaspica AHE extract might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity.     

Significant curative functions of the mesenchymal stem cells on methotrexate‐induced kidney and liver injuries in rats

Mesenchymal stem cells (MSCs) curative effects on methotrexate (MTX)‐induced kidney and liver injuries remain elusive. Therefore, rats were divided into five groups, rats received MTX orally (14 mg/kg) as a single dose/week for 2 weeks, groups 3 and 4 were injected once with 2 × 10⁶ cells bone marrow MSCs and adipose‐derived MSCs, respectively. The last group administered dexamethasone (DEX) (0.5 mg/kg, p.o) for 7 days. MTX caused marked increase in malondialdehyde and nitrite/nitrate concentrations. However, MTX administration decreased reduced glutathione content plus catalase activity. In addition, MTX caused a significant increment in kidney and liver biomarkers levels. Moreover, MTX showed renal tubules vacuolation and necrosis of hepatocytes, as well expression of caspase‐3 and nuclear factor kappa beta in kidney and liver tissues were observed. MSCs treatment alleviated previous side effects induced by MTX. MSCs improved nephrotoxicity and hepatotoxicity induced by MTX to a better extent as compared with DEX.     

Alpha lipoic acid prevents doxorubicin‐induced nephrotoxicity by mitigation of oxidative stress,inflammation, and apoptosis in rats

This study aimed to evaluate the protective effects of alpha lipoic acid (ALA) against doxorubicin (DOX)‐induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg i.v.) induced nephrotoxicity evidenced by significant elevations in kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha, and renal contents of malondialdehyde, nitric oxide, cyclooxygenase‐2, and caspase‐3. Also, it causes significant reduction in final body weight, serum albumin, renal contents of reduced glutathione and superoxide dismutase activity. Histopathological changes in the kidney tissue confirmed the nephrotoxic effect. In contrast, pretreatment with ALA (50 mg/kg, orally) for 14 days before DOX and for 7 days after DOX administration mitigated renal toxicity evidenced by greater improvement in the examined oxidative stress, inflammation, and apoptosis parameters. In conclusion, ALA had promising protective effects against DOX‐induced nephrotoxicity that might be attributed to its antioxidant, anti‐inflammatory, and antiapoptoic activities.     

Renin-angiotensin system inhibitors combined with cisplatin exacerbate cisplatin-induced nephrotoxicity in mice

IntroductionWe previously reported that the concomitant use of enalapril and telmisartan exacerbates the risk of cisplatin (CDDP)-induced acute renal dysfunction compared to other antihypertensive drugs in mice. Thus, in the current study, we investigated the risk of developing chronic kidney disease following repeated concomitant use of CDDP and antihypertensive drugs.Materials and MethodsMale BALB/c mice were divided into 12 groups: (1) Control group (untreated), (2) CDDP group (7 mg/kg, CDDP), (3) AML group (5 mg/kg, amlodipine), (4) ENA group (2.5 mg/kg, enalapril), (5) TEL group (10 mg/kg, telmisartan), (6) LOS group (10 mg/kg, losartan), (7) CDDP+AML group (5 mg/mL, AML), (8) CDDP+ENA group (2.5 mg/kg, ENA), (9) CDDP+LowENA group (1.25 mg/kg, ENA), (10) CDDP+TEL group (10 mg/kg, TEL), (11) CDDP+LowTEL group (5 mg/kg, TEL), and (12) CDDP+LOS group (10 mg/kg, LOS). CDDP was administered intraperitoneally four times every 7 days, and each antihypertensive drug was administered orally from day 3 before CDDP administration until day 24 (six times a week). The degree of renal damage was assessed. The nephrotoxicity of each individual was evaluated by measuring serum creatinine and blood urea nitrogen levels. The degrees of renal fibrosis and epithelial-mesenchymal transition were also examined in kidney tissue sections.Results and DiscussionThe results suggest that combinatorial treatment of CDDP and renin-angiotensin system inhibitors, particularly ENA and TEL, may exacerbate CDDP-induced nephrotoxicity. This study clearly demonstrates the need for large-scale clinical studies to construct treatment regimens that do not interfere with the therapeutic intensity of CDDP.     

Antioxidant-rich date palm fruit extract inhibits oxidative stress and nephrotoxicity induced by dimethoate in rat

Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, the antioxidant effect of date palm fruit extract on dimethoate-induced oxidative stress and nephrotoxicity in rat is investigated and compared with the effect of the well-known antioxidant vitamin C. Male Wistar rats were randomly divided into six groups of ten each: a control group (C), a group that received dimethoate (20 mg/kg body weight) (D), a group given Deglet Nour extract (DNE), a group treated with DNE 30 min before the administration of dimethoate (DNE + D), a group which received VitC (100 mg/kg body weight) plus dimethoate (Vit C + D), and a group given dimethoate for the first month and DNE 30 min after administration of dimethoate, during the second month (D + DNE). These components were daily administered by gavage for 2 months. After completing the treatment period, blood samples from rats were collected under inhaled diethyl ether anesthesia for serum urea, uric acid, and creatinine levels, while the rat kidneys were obtained for enzyme assays and histology. Oral administration of dimethoate in rats induced a marked renal failure characterized by a significant increase in serum creatinine and urea levels (p < 0.01) in addition to a significant decrease in serum uric acid (p < 0.05). Interestingly, these drastic modifications were accompanied by a marked enhancement of lipid peroxidation in kidney, indicating a significant induction of oxidative damage (p < 0.01) and dysfunctions of enzymatic antioxidant defenses. These biochemical alterations were also accompanied by histological changes in kidney revealed by a narrowed Bowman’s space, tubular degeneration, tubular cell desquamation, and tubular dilatation of proximal tubules. Treatment with date palm fruit extract (Deglet Nour) and also with vitamin C significantly (p < 0.05) reversed the serum renal markers to their near-normal levels when compared with dimethoate-treated rats. In addition, Deglet Nour extract and vitamin C significantly reduced lipid peroxidation, restored the antioxidant defense enzymes in the kidney, and improved the histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress-induced nephrotoxicity.     

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in kidney of rats treated with gentamicin sulphate

The protective effects of Panax ginseng (PG) on gentamicin sulphate (GS) induced acute nephrotoxicity were investigated in rats. A total of 32 adult Sprague-Dawley rats were randomly divided into 4 equal groups and treated by intraperitoneous route for 10?days with: 0.5?mL of isotonic saline (group C), GS 100?mg/kg/day (group GS), co treatment PG (100 and 200?mg/kg/day) plus GS (100?mg/kg/day). After the last injection, kidney markers (urea, creatinine and blood urea nitrogen-BUN) and hepatic markers (aspartate aminotransferase-AST, alanine aminotransferase-ALT, gama glutamil transferase-GGT), and biochemical parameters were analyzed using diagnostic kits. Also, kidney changes were evaluated by immunohistochemical and stereological methods. GS treatment induced significant elevation (P?相似文献   

Protective Effects of Curcumin against Sodium Fluoride-Induced Toxicity in Rat Kidneys

In the present study, the protective effect of curcumin against sodium fluoride-induced nephrotoxicity was evaluated in rats. Renal injury was induced by daily administration of 600 ppm sodium fluoride in drinking water for 1 week. One week before the administration of fluoride, the animals selected as study group were given curcumin (10 and 20 mg/kg body weight, intraperitoneally). After 1 week, lipid peroxidation level, activities of superoxide dismutase, catalase, and level of glutathione in kidney homogenate were measured. Blood serum samples were examined for creatinine, serum urea, and blood urea nitrogen levels. Another group of rats received vitamin C (10 mg/kg) as standard antioxidant. The results show that curcumin and vitamin C treatment prior to fluoride administration normalized the levels of serum creatinine, serum urea, and blood urea nitrogen. Moreover, curcumin and vitamin C administrations prevented the antioxidant enzyme decreasing and lipid peroxidation levels imbalance. In conclusion, curcumin treatment at the doses of 10 and 20 mg/kg (intraperitoneally) showed significant nephroprotective effects.     

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.     

Protective effect of cilostazol against doxorubicin-induced cardiomyopathy in mice

Doxorubicin (Dox) is an effective anti-cancer drug, but its use is limited because of its adverse effect of inducing irreversible dilated cardiomyopathy. Cilostazol (Cilo), a potent phosphodiesterase III inhibitor, has been reported to have an anti-inflammatory effect. Here, we investigated whether Cilo has a protective effect against Dox-induced cardiomyopathy (DIC). Mice were randomly divided into four groups: saline control, Dox (15 mg/kg), Dox (15 mg/kg) plus Cilo (50 mg/kg), and Cilo (50 mg/kg). The results showed that the coadministration of Dox and Cilo significantly enhanced left-ventricular systolic function compared with Dox alone. In addition, Cilo treatment significantly reduced Dox-induced perivascular fibrosis, collagen concentration, and connective growth factor expression in the heart. Also, Cilo administration markedly reduced Dox-induced levels of serum B-type natriuretic peptide, dysferlin, high-mobility group protein B1, Toll-like receptor 4, nuclear factor-κB p65, and cyclooxygenase-2. Furthermore, Cilo treatment significantly reduced Dox-induced oxidative stress by lowering the translocation of Nrf2 into the nucleus and the expression of NQO1, heme oxygenase 1, and superoxide dismutase-1. Our results suggest that Cilo may be a potential antifibrotic, antioxidative, and anti-inflammatory drug for DIC.     

Chamomile flower extract ameliorates biochemical and histological kidney dysfunction associated with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in females of childbearing age and research findings have revealed a potential association between PCOS and renal dysfunction. This study aimed to investigate renal dysfunction that might be associated with PCOS in rats and to evaluate the potential protective effect of chamomile against PCOS complicated by kidney damage. A rat model of PCOS was induced by injecting estradiol valerate (0.2 mg/rat × 2) into adult virgin female rats. Rats were treated with either ethyl alcohol extract of chamomile flower (75 mg/kg/day) or metformin (Met) (500 mg/kg/day). Induction of PCOS was associated with increased relative right kidney weight percentage and increased serum levels of urea, lipid peroxide product, and testosterone. PCOS was also associated with increased p53 expression in kidney glomeruli and medullary tubules with decreased Bcl2 expression in kidney glomeruli. Administration of chamomile extract significantly decreased levels of serum urea, testosterone, and lipid peroxide product, and p53 expression in kidney glomeruli and tubules. The extract significantly increased levels of antioxidant markers levels (reduced glutathione, catalase, and superoxide dismutase) and the expression of the anti-apoptotic gene Bcl2. Conversely, administration of Met did not improve serum levels of urea. Met also exerted no pronounced effect on p53 gene expression. The results of this study highlight the importance of monitoring kidney function in patients with PCOS and investigating the associated underlying mechanism. Chamomile extract was found to ameliorate kidney damage associated with PCOS through antioxidant, testosterone-lowering, and anti-apoptotic mechanisms.     

Epigallocatechin-3-gallate protects against cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis

Cisplatin (CP)-induced nephrotoxicity hampers its application in clinic. Green tea, particularly its predominant polyphenolic constituent epigallocatechin-3-gallate (EGCG), possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. The present study was designed to investigate the protective effects of EGCG against CP-induced nephrotoxicity in mice. Male C57/BL6 mice in different groups received single injection of CP (20 mg/kg) and EGCG (100 mg/kg) in various sets and kidney tissues and blood were collected after killing. Then, samples were used for biochemical and immunohistochemical assay. Our results showed EGCG decreased biochemical factors and immunohistochemical damage induced by CP. Besides, expression of phosphorylated-extracellular signal-regulated kinase (p-ERK), glucose-regulated protein 78 (GRP78), caspase-12, and apoptosis of kidney were decreased by EGCG via inhibition of endoplasmic reticulum (ER) stress-induced apoptosis.     

Diacerein ameliorates kidney injury induced by cisplatin in rats by activation of Nrf2/Ho-1 pathway and Bax down-regulation

Cisplatin is an antineoplastic medicine used for solid tumor treatment. The main side effect that limits its dose is nephrotoxicity. Diacerein has been used for the treatment of joint diseases like osteoarthritis. It also has exhibited analgesic effects and antipyretic activities in animal models so this study targets to indicate the diacerein effect on nephrotoxicity induced by cisplatin in rats. Rats were distributed into four groups: normal healthy control; diacerein, which received diacerein daily by gastric gavage (50 mg/kg/day); cisplatin, which received only one intraperitoneal injection of cisplatin (6 mg/kg) and cisplatin and diacerein, which received diacerein daily after the cisplatin injection till 7th and 12th days, respectively. Diacerein treatment decreased kidney function markers so the cisplatin effect was reversed. Also, diacerein increased the renal antioxidants and decreased oxidative stress. Diacerein up-regulated Ho-1 (heme oxygenase 1), Nrf2 (Nuclear factor erythroid 2–related factor 2) and endothelial nitric oxide synthase (eNOS) genes expression, while down-regulated Bcl-2-associated X protein (Bax) gene expression. Furthermore, the renal transforming growth factor beta-1 (TGF-β1) decreased by the diacerein effect. Consequently, diacerein has a curative effect against cisplatin due to its anti-inflammatory, antioxidant, and antiapoptotic properties.     

Renoprotective effects of montelukast in an experimental model of cisplatin nephrotoxicity in rats

Renal toxicity is one of the most severe complications that can occur with cisplatin (CIS) administration in cancer patients. Montelukast (ML) renoprotective outcome contrary to CIS‐drawn nephrotoxicity remains obscure. Therefore, adult male Sprague–Dawley rats were orally given ML (10 and 20 mg/kg/day) 5 days before and after single CIS (5 mg/kg; i.p.) treatment. ML returned blood urea nitrogen, as well as serum creatinine and gamma glutamyl transferase that were elevated by CIS to normal level. The improved kidney function tests corroborated the attenuation of CIS renal injury at the microscopical level. It also reduced serum/renal nitric oxide and renal hemeoxygenase‐1. Meanwhile, ML hindered the raised levels of serum endothelin‐1, serum and renal tumor necrosis factor‐α, and monocyte chemoattractant protein‐1. These effects were associated by deceased caspase‐3 expression in kidney after ML treatment. In conclusion, ML guards against CIS‐induced nephrotoxicity via anti‐inflammatory and antiapoptotic properties.     

Naringenin ameliorates Cyclophosphamide-induced nephrotoxicity in experimental model

Cyclophosphamide (CP) is widely described in the management of several nonneoplastic and neoplastic disorders. Renal damage is the most reported toxic effect of CP in clinical practice.Our study aimed to evaluate the effect of Naringenin (NG) in attenuating renal damage induced by CP in an experimental model.A total of 32 rats were divided into four groups (n = 8): negative control: rats fed on a basal diet, positive control: rats injected intraperitoneally with CP 50 mg/kg of body weight/day, NG 100: rats treated with NG 100 mg/kg/day body orally with concomitant administration of CP as described before, and NG 200: rats treated with NG 200 mg/kg/day body orally daily + CP. At the end of the experimental protocol (21 days), blood creatinine and urea levels were measured. The antioxidant activities and lipid peroxidation products were measured in the renal tissues as indicators of oxidative damage. Histopathological examination and immunohistochemistry staining were also performed on renal tissues.Coadministration of NG along with CP significantly (p < 0.001) improved the renal function and antioxidant capacities compared with positive control animals. Furthermore, histopathological, and immunological examination of renal tissue confirmed the protective effect of NG against CP-induced nephrotoxicity.The current study showed that NG has the potential to protect CP-induced renal damage, which may be beneficial for further studies and the design of NG analogs to be useful in clinical practice against CP-induced nephrotoxicity.     

Phytochemical analysis and toxicological evaluation of the ethanolic Leaves extract of Hypoestes rosea on the morphology and biochemical indices of the Kidneys of albino Wistar Rats

BackgroundHypoestes rosea (family: Acanthacea), has been harnessed and utilized for treatment of several ailments. However, there is the paucity of available data on nephrotoxicity associated with this herb. Here, we investigated the phytochemical profile and toxicological effect of H. rosea on Wistar Rats.MethodsTwenty rats (weight range: 75–100 g) were assigned into five study groups, viz; (a) control (without treatment) (b) treatment group 1, orally administered with 50 mg/kg (c) treatment group 2, orally administered with 100 mg/kg (d) treatment group 3, orally administered with 250 mg/kg, and (e) treatment group 4, orally administered with 300 mg/kg of H. rosea, respectively for 28 days of four rats per group. The rats were made unconscious by using oral administration of chloroform. Cardiac punctures were made, and blood samples collected into 10 ml labeled plain container, allowed to clot and spun to harvest serum for determination of sodium, potassium, chloride, bicarbonate, urea and creatinine using colorimetric, back-titrimetric, Urease-Berthelot and Jaffe’s reaction methods respectively. Kidneys of rats were harvested, weighed and immediately fixed in 10% neutral buffered formalin for histological analysis.ResultMean serum sodium (p = 0.049), potassium (p = 0.007), and urea (p < 0.001) levels were significantly higher among the treatment groups compared to controls. Histopathological findings of kidney sections revealed mild glomerular infiltration in treatment groups 2–4. Additionally, sclerosis was observed in groups 3–4. Phytochemical analysis of H. rosea revealed presence of alkaloids, flavonoids, saponins, tannins, terpenoids, steroids and reducing sugars.ConclusionFrom the findings in this study, H. rosea leaf extract causes significant damage to the kidneys of Wistar rats at higher doses. Of which, the damages were dose-dependent in direct proportionality manner. To better determine the safe dosage and ideal duration of consumption, there is the need for further studies on H. rosea.     

Protection against cisplatin-induced nephrotoxicity by Cu(II)2(3,5-diisopropylsalicylate)4

The ability of Cu(II)(2)(3,5-diisopropylsalicylate)(4), CuDIPS, which exhibits superoxide dismutase (SOD)-like activity, to prevent cisplatin-induced nephrotoxicity was examined in rats. Rats were divided into four groups and treated as follows: (i) vehicle control; (ii) cisplatin (16 mg/kg, intraperitoneally); (iii) CuDIPS (10 mg/kg, intraperitoneally); and (iv) cisplatin plus CuDIPS. Rats were sacrificed 3 days post-treatment. Cisplatin alone resulted in significantly increased plasma creatinine and urea. Administration of 10 mg/kg CuDIPS prevented the cisplatin-induced elevation of plasma creatinine and urea and protected against kidney damage. Relative to controls, rats that received cisplatin treatment displayed a decrease of reduced glutathione (GSH) and elevated platinum and thiobarbituric acid reactive substances (TBARS) levels in the kidney. In comparison with controls, activities of antioxidant enzymes (SOD, CAT, GSH-Px and GSH-Rd) were also reduced in the kidney of rats treated with cisplatin. Administration of 10 mg/kg CuDIPS prevented cisplatin-induced alterations in renal platinum, GSH, TBARS, and antioxidant enzyme activities. This study suggests that the protection offered by CuDIPS against cisplatin-induced nephrotoxicity is partly related to maintenance of renal antioxidant systems.     

Hepatoprotective and antioxidant activity of N-Trisaccharide in different experimental rats

ObjectivesTo investigate the hepatoprotective, antioxidant and antihyperlipidemic effect of N-Trisaccharide isolated from Cucumis prophetarum (L.) on different experimental rats.MethodsN-Trisaccharide (25 and 50 mg/kg.b.w), silymarin (25 mg/kg) and glibenclamide (25 mg/kg) was orally administered once daily for 28 days and toxicity evaluation studies were carried out. Liver damage was assessed by determining DNA damage, serum enzyme activities and hepatic histopathology of carbon tetrachloride (CCl₄) induced hepatic injury in rats. Enzymatic and non enzymatic antioxidant levels in liver and kidney were determined and biochemical parameters such as, serum lipid profile, renal function markers were estimated in type 2 diabetic rats.ResultsDNA fragmentation analysis revealed the protective effect of N-Trisaccharide on liver DNA damage. Histopathological studies indicated that CCl₄-induced liver injury was less severe in N-Trisaccharide (25 and 50 mg/kg) treated group. Given at the above doses conferred significant protection against the hepatotoxic actions of CCl₄ in rats, reducing serum markers like SGOT, SGPT, ALP, creatinine and urea levels back to near normal (p < 0.05) compared to untreated rats. In diabetic rats, N-Trisaccharide treatment significantly reversed abnormal status of enzymatic and non-enzymatic antioxidants levels to near normal. Also, serum lipids such as TG, TC, LDL-C and VLDL-C levels were significantly (p < 0.05) reduced compared to diabetic untreated rats.ConclusionPresent study results confirm that N-Trisaccharide possesses significant antihyperlipidemic, antioxidant and hepatoprotective properties.     

Renal protective effects of arjunolic acid in a cisplatin-induced nephrotoxicity model

Cisplatin is the first platinum-containing anti-cancer drugs. Cisplatin notable side effect of nephrotoxicity limits its use in clinic. Meanwhile, arjunolic acid possesses anti-inflammatory properties and plays protective roles against chemically induced organ pathophysiology. This study was conducted to find out whether arjunolic acid could attenuate kidney damage in rats, and to elucidate its possible mechanism of action. Fifty rats were treated with cisplatin (10 mg/kg) in the presence/absence of 100 or 250 mg/kg arjunolic acid. Arjunolic acid is given 1 h after cisplatin. Morphological changes were assessed in kidney sections stained with Hematoxylin/Eosin and Masson Trichrome. Kidney samples were used for measurements of transforming growth factor (TGF)-β1 and its type 1 receptor (TGF-βR1), tumor necrosis factor (TNF)-α and interleukin (IL)-1β by ELISA. Gene expression NFκB was determined by real time-PCR. Kidney tissue apoptosis was assessed by measuring the activities of caspase-3/8/9. The renal protective effect of arjunolic acid was confirmed by approximately normal appearance of renal tissue and the relatively unaffected serum creatinine and urea levels. Furthermore, arjunolic acid showed dose dependent reduction in cisplatin-induced elevation in renal levels of TGF-βR1, TGF-β1, TNF-α, IL-1β and caspases. These findings demonstrated that arjunolic acid attenuates cisplatin nephrotoxicity either indirectly by enhancing body antioxidant activity or directly through several mechanisms, including inhibition of pro-inflammatory cytokines, blocking activation of TGF-β1, and anti-apoptotic effects.