Diphenyl diselenide is as effective as Ebselen in a juvenile rat model of cisplatin-induced nephrotoxicity

BackgroundCisplatin (CIS) is widely used in the chemotreatment of pediatric tumors. However, the CIS use is limited because of its high incidence of toxicity, mainly nephrotoxicity. Although there are many studies about CIS-related nephrotoxicity in animal models, only a few studies focus on juvenile animals. Because redox disturbances have been associated with kidney damage induced by CIS, this study aimed to compare the effectiveness of Ebselen and diphenyl diselenide (PhSe)₂ against nephrotoxicity induced by CIS in juvenile rats.MethodsJuvenile Wistar rats were randomly divided into six groups: rats from groups I to III received an intraperitoneal (i.p.) injection with saline solution. The other groups received CIS (i.p., 6 mg/kg) on the first day. One hour before CIS injection and on the next four days, animals of groups III and V were intragastrically treated with Ebselen (11 mg/kg) whereas those from groups IV and VI received (PhSe)₂ (12 mg/kg). After 24 h of the last treatment, blood and kidney were collected, and the parameters of renal function and oxidative stress were determined.ResultsKidney damage induced by CIS was confirmed by the increase of creatinine, urea and uric acid levels in the blood of juvenile rats. The renal oxidative disturbance was characterized by an increase in the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl, and nitrogen oxides (Nox), as well as the decrease in non-protein thiol content (NPSH), glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) activities. CIS inhibited the activities of δ-aminolevulinic acid dehydratase (δ-ALA-D) and Na⁺, K⁺-ATPase and down-regulated the Nrf2/Keap-1/HO-1 pathway in the kidney of juvenile rats.ConclusionBoth Ebselen and (PhSe)₂ modulated back to the normal levels all parameters altered by the CIS administration in the kidney of juvenile rats. Thus, this study shows that (PhSe)₂ was as effective as Ebselen in protecting the kidney against oxidative damage caused by CIS in rats.     

Effects of Aronia melanocarpa and Hypericum perforatum aqueous extracts on hexavalent chromium induced toxicity in rat’s thyrocytes

BackgroundHexavalent chromium known as oxidizing agent is able to form reactive oxygen species. Aronia melanocarpa and Hypericum perforatum are two plants known for their antioxidant effects. Our study aimed to establish if CrVI induces apoptosis and structural changes in thyrocytes and if its effect can be counteracted by the administration of both extracts.Materials and methodsWistar rats divided in five groups: C - distilled water (DW), Cr – 75 mg/L CrVI in DW for 3 months, Cr 2 – 75 mg/L CrVI in DW for 3 months followed by 1 month DW, CrA – 3 months 75 mg/L CrVI in DW and 1 month Aronia 2.5% extract, CrH – 3 months 75 mg/L CrVI in DW and 1 month Hypericum 2.5% extract. Histological assessment and qRT-PCR for evaluation of BAX and Bcl2 protein levels performed on thyroid samples.ResultsThe Cr and Cr2 groups were those with altered cytoarchitecture: increase in the diameter of many thyroid follicles, a decrease in their number, a decrease in the height of the follicular cells. The histological examination of the CrH group revealed almost recovery of structural architecture. The BAX gene levels were higher in the Cr and Cr2 groups indicating the apoptotic activity of chromium. In extract receiving groups the BAX gene expressions were significantly lower, but the lowest level presented the CrH group. Bcl2 gene expression levels indicate antiapoptotic activity being elevated in the Cr group, followed by CrA, Cr2, and CrH groups. The BAX/Bcl2 ratio which significantly increased in the case of the Cr and Cr2 group compared to the groups that were administered the two plant extracts.ConclusionThe results obtained in this study confirm that CrVI has toxic effects on thyroid endocrine cells and H. perforatum has stronger antioxidant properties against the action of hexavalent chromium in thyrocytes than A. melanocarpa.     

Pycnogenol prevents potassium dichromate (K2Cr2O7)-induced oxidative damage and nephrotoxicity in rats

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. Recent evidence indicates that Pycnogenol^® (PYC), French maritime pine bark extract, exhibits antioxidant potential and protects against various oxidative stressors. The aim of the present study was to examine the modulating impacts of PYC on potassium dichromate (K₂Cr₂O₇)-induced oxidative damage and nephrotoxicity in rats. Male Wistar rats were divided into four groups. The first group was control, the second group was control plus pre-treated with PYC (10 mg/kg, body weight; in saline; intraperitoneally; once daily for 3 weeks) as drug control and the third group was saline pre-treated plus treated with a single injection of K₂Cr₂O₇ (15 mg/kg, body weight; in saline; intraperitoneally) as toxicant group. The fourth group was PYC pre-treated plus K₂Cr₂O₇ injected. Forty-eight hours after K₂Cr₂O₇-treatment, blood was drawn for estimation of renal injury markers in serum. Rats were then sacrificed, and their kidneys were dissected for biochemical and histopathological assays. K₂Cr₂O₇-treated rats showed significant increases in markers of renal injury in serum, including blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), which were significantly (P < 0.05) decreased by PYC pre-treatment. Moreover, prophylactic pre-treatment of rats with PYC significantly (P < 0.05) ameliorated increased thiobarbituric reactive substances (TBARS), malonaldehyde (MDA) and protein carbonyl (PC), and decreased levels of glutathione (GSH) and catalase activity in the kidney homogenate of K₂Cr₂O₇-treated rats. These results were also supported and confirmed with histopathological findings. The study suggests that PYC is effective in preventing K₂Cr₂O₇-induced oxidative mediated nephrotoxicity, but more studies are needed to confirm the effects of PYC as a nephroprotective agent.     

The potential effects of pomegranate (Punica granatum) juice on carbon tetrachloride-induced nephrotoxicity in rats

The purpose of this study was to evaluate the effect of pomegranate (Punica granatum) in inhibiting and reversing the nephrotoxicity of carbon tetrachloride, a potent oxidative stress inducer which induces cellular kidney damage. Rats were intraperitoneally injected with carbon tetrachloride (2 mL/kg body weight) which produced severe renal tissue damage, as demonstrated by decreased uric acid and dramatic elevation of urea and creatinine. In addition, carbon tetrachloride injection caused oxidative stress in rats, as evidenced by increased lipid peroxidation and nitrite/nitrate (NO _x ) concentrations in the renal tissue, along with a remarkable reduction in superoxide dismutase, catalase, glutathione transferase, glutathione reductase, glutathione peroxidase activities and glutathione content. We suggested that pomegranate juice was able to elevate the antioxidant defense system, clean up free radicals, lessen oxidative damages and protect the kidney against carbon tetrachloride-induced toxicity, thus having a potential protective effect.     

Peperomia pellucida (L.) Kunth as an angiotensin-converting enzyme inhibitor in two-kidney,one-clip Goldblatt hypertensive rats

BackgroudPeperomia pellucida (L.) Kunth has been used widely to treat headache, kidney disease, fever, and hypertension. Previous in vitro studies discovered that the flavonoid-rich extract of this plant has potential hypotensive effects, specifically angiotensin-converting enzyme (ACE)-inhibitory activity. However, there is insufficient scientific evidence to validate the result in vivo.PurposeThis study investigated the dose dependencies of the effects of the ethyl acetate fraction of the ethanolic extract of this plant on blood pressure and biomarkers associated with the renin–angiotensin–aldosterone systems (RAAS), such as angiotensin II (AII) and the plasma renin concentration (PRC).Study designIn total, 30 two-kidney, one-clip (2K1C) hypertensive model rats were divided into five groups (n = 6 each): model group, captopril 25 mg/kg BW group, and three different ethyl acetate groups (25, 50, and 100 mg/kg BW). Another six rats comprised the sham group.MethodsRenal hypertensive rats (RHRs) were generated using stainless steel modification clips. Drugs were administered via oral gavage for 2 consecutive weeks. Blood pressure was measured weekly prior to treatment. Blood samples were collected before treatment and after the last dose to measure AII and PRC. The left kidney was isolated for histopathological examination.ResultsBlood pressure, AII levels, and PRC were elevated after 6 weeks in RHRs. Treatment with captopril and the ethyl acetate fraction of P. pellucida (L.) Kunth decreased blood pressure, AII levels, and PRC. The ethyl acetate fraction at a dose of 50 mg/kg BW had similar ACE-inhibitory effects as captopril. Histopathological examination disclosed coagulative necrosis in clipped kidneys. Impairment was alleviated in a dose-dependent manner by P. pellucida (L.) Kunth, similarly as observed in the captopril group.ConclusionP. pellucida (L.) Kunth targets the renin–angiotensin–aldosterone system, which might explain its antihypertensive effects.     

Neuroprotective Effect of <Emphasis Type="Italic">Rosmarinus officinalis</Emphasis> Extract on Human Dopaminergic Cell line,SH-SY5Y

Hydrogen peroxide (H₂O₂) is a major Reactive Oxygen Species (ROS), which has been implicated in many neurodegenerative conditions including Parkinson’s disease (PD). Rosmarinus officinalis (R. officinalis) has been reported to have various pharmacological properties including anti-oxidant activity. In this study, we investigated the neuroprotective effects of R. officinalis extract on H₂O₂-induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that H₂O₂-induced cytotoxicity in SH-SY5Y cells was suppressed by treatment with R. officinalis. Moreover, R. officinalis was very effective in attenuating the disruption of mitochondrial membrane potential and apoptotic cell death induced by H₂O₂. R. officinalis extract effectively suppressed the up-regulation of Bax, Bak, Caspase-3 and -9, and down-regulation of Bcl-2. Pretreatment with R. officinalis significantly attenuated the down-regulation of tyrosine hydroxylase (TH), and aromatic amino acid decarboxylase (AADC) gene in SH-SY5Y cells. These findings indicate that R. officinalis is able to protect the neuronal cells against H₂O₂-induced injury and suggest that R. officinalis might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.     

Secoisolariciresinol diglucoside protects against cadmium-induced oxidative stress-mediated renal toxicity in rats

BackgroundCadmium is a well known environmental pollutant and strong toxic heavy metal, that causes oxidative damage to various organs of the body, including the kidney. Cadmium (II) chloride (CdCl₂) is a water-soluble crystalline form, which exhibits a higher affinity with chlorides at the target site. The current study examined the protective effects of Secoisolariciresinol diglucoside (SDG), a principal lignan extracted from flaxseeds against CdCl₂-induced renal toxicity in rats.MethodsTwenty four healthy male Wistar rats with four groups of six animals each were used in the study. Group-1- Control was administered with saline. Group-2 –was treated with SDG; Group-3 with CdCl₂ alone, and Group-4 were treated with CdCl₂ plus SDG. The effect of Cd on kidney was assessed in terms of various parameters like lipid peroxidation, production of Nitric oxide (NO) and Myeloperoxidase (MPO), and kidney function markers like uric acid, urea, and creatinine. The levels of antioxidant molecules like glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were also measured, apart from histopathological studies.ResultsThe animals that received CdCl₂, exhibited changes in the concentration of Cd in the kidney. The levels of kidney function markers like uric acid, urea, and creatinine were found to be abnormal in serum, and also there was a drastic decrease in the levels of glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The treatment of SDG significantly decreased (p < 0.05) the levels of NO and MPO in the animals treated with CdCl₂ plus SDG when compared to the animal group treated with CdCl₂ alone. The treatment of SDG before CdCl2 injection exhibited significant changes in the activity of the antioxidant enzymes, which was evidenced by the restoration in their activities, when compared to CdCl2 alone treated group (p < 0.05), as observed in the results of histopathology.ConclusionsThe findings of the present investigation suggested that SDG exhibited anti-oxidant, anti-apoptotic and renoprotective properties. Thus, SDG may act as a supramolecular binding component and naturally occurring metal chelating agent for metal cations like Cd²⁺. Therefore, flaxseed lignan-SDG can be used as a therapeutic agent against nephrotoxicity caused by cadmium. However, detailed future studies are needed to know the underlying mechanism of action of SDG against the Cd and other heavy metals induced nephrotoxicity.     

Protective effects of grape seed proanthocyanidins against iron overload-induced renal oxidative damage in rats

BackgroundExcessive exposure to iron can cause kidney damage, and chelating drugs such as deferoxamine and deferiprone have limited usefulness in treating iron poisoning. This study was designed to investigate the protective effects of grape seed proanthocyanidins (GSPAs) against iron overload induced nephrotoxicity in rats. The roles of GSPAs in chelating iron, antioxidant activity, renal function, pathological section, and apoptosis-related gene expression were assessed.MethodsNewly weaned male Sprague–Dawley rats aged 21 days (weight, 65 ± 5 g) were randomly divided into four groups containing 10 rats each: normal control (negative) group, iron overload (positive) group, GSPAs group, and GSPAs + iron overload (test) group. Iron dextran injections (2.5 mg⋅ kg⁻¹) and GSPAs (25 mg⋅ kg⁻¹) were intraperitoneally and intragastrically administered to rats daily for 7 weeks, respectively. Measurements included red blood cell (RBC) count and hemoglobin (Hb) level, serum total iron-binding capacity (TIBC), renal iron content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant activity (T-AOC), creatinine (CR) and blood urea nitrogen (BUN) levels, pathological changes, and apoptotic Fas, Bax expressions in the kidney tissue. Differences among the dietary groups were determined using one-way analysis of variance with post-hoc Tukey’s test. P < 0.05 was considered statistically significant.ResultsRBC count, Hb level, renal iron content, MDA content, CR and BUN levels, and Fas, Bax expressions significantly increased in the positive group than in the negative group; contrarily, TIBC, GSH-Px activity, and T-AOC significantly decreased in the positive group than in the negative group (P < 0.05). Although not statistically significant, SOD activity was slightly reduced in the positive group than in the negative group. Inflammatory cell infiltration and fibrous tissue proliferation were observed in the kidney tissue of the rats in the positive group; in contrast, the rats exhibited better recovery when GSPAs were used instead of iron alone. Compared with the positive group, RBC counts, Hb levels, renal iron contents, the MDA content, CR and BUN levels, and Fas, Bax expressions significantly decreased, whereas the TIBC, the GSH-Px and SOD activities as well as T-AOC significantly increased in the test group rats (P < 0.05). There were no significant differences in the RBC counts, Hb levels, TIBC, renal iron contents, the SOD activity and MDA content, CR and BUN levels, and Fas expression between the GSPAs and negative groups. The GSH-Px activity and T-AOC were significantly increased whereas Bax expression was significantly decreased in the GSPAs group rats than in the negative group rats (P < 0.05). The rats in the GSPAs, test, and negative groups displayed glomeruli and tubules with a clear structure; further, the epithelial cells in the renal tubules were neatly arranged.ConclusionsGSPAs have protective effects on nephrotoxicity in rats with iron overload. Thus, further investigation of GSPAs as a new and natural phytochemo-preventive agent against iron overload is warranted.     

Nephroprotective,cytotoxic and antioxidant activities of Euphorbia paralias

ObjectiveTo investigate the effect of the ethyl acetate fraction of the aerial parts of E. paralias L. F. Euphorbiaceae on nephroprotective, cytotoxic, and antioxidant.Methodsdifferent spectroscopic and spectrophotometric methods were applied to identify phytoconstituents. The nephroprotective potential of E. paralias ethyl acetate fraction (Ep EtOAc) was evaluated in male rats with thioacetamide-induced kidney injury, as wll as cytotoxic activity was evaluated using a viability assay, and the antioxidant activity was evaluated using the DPPH method. Results: quantitative estimation of total phenolics and flavonoids of E. paralias was performed using unique spectrophotometric methods. The polyphenolic compounds gallic acid (1), ellagic acid (2), kaempferol-3-O-(6″-O-galloyl-β-D-glucopyranoside) (3), quercetin-3-O-β-D-glucopyranoside (4) and quercetin-3-O-β-D-arabinoside (5) were isolated from the ethyl acetate fraction of the aerial parts of E. paralias. The thioacetamide administration resulted in marked nephrotoxicity, but pretreatment with Ep EtOAc significantly attenuated the nephrotoxicity through alteration of kidney biomarkers, thereby improving the redox status of the tissue and restoring serum biochemical parameters nearly to normal levels. This study revealed a significant cytotoxic and strong antioxidant effect. Conclusion: we conclude that the Ep EtOAc may be used in the future as nephroprotective, cytotoxic, and antioxidant agent derived from a natural source.     

Ameliorative effect of kaempferol,a flavonoid,on oxidative stress in streptozotocin-induced diabetic rats

Abstract

Objective

The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats.

Methods

Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats.

Results

The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal.

Conclusion

The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.     

Hypoglycemic and hepatoprotective activity of Rosmarinus officinalis extract in diabetic rats

The present study examined the effect of water extract (200 mg/kg body weight) of Rosmarinus officinalis L. in streptozotocin (STZ)-induced diabetic rats for 21 days. The hepatoprotective effects were investigated in the liver tissues sections. There was a significant increase in serum liver biochemical parameters (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase), accompanied by a significant decrease in the level of total protein and albumin in the STZ-induced rats when compared with that of the normal group. The high-dose treatment group (200 mg/kg body wt) significantly restored the elevated liver function enzymes near to normal. This study revealed that rosemary extracts exerted a hepatoprotective effect. The results indicate that the extract exhibits the protective effect on tissues and prove its potentials as an antidiabetic agent.     

Protective effect of rosemary (Rosmarinus officinalis) against diethylnitrosamine-induced renal injury in rats

Abstract

Context: The kidney plays a central role in detoxification and excretion of toxic metabolites, and therefore, is susceptible to toxicity by xenobiotics.

Objective: To investigate the protective effect of Rosmarinus officinalis (rosemary) powder and its essential (volatile) oil against diethylnitrosamine (DEN)-induced renal injury in rats.

Materials and methods: Phenolic and flavonoid components were characterised in rosemary powder using HPLC-UV instrument while rosemary essential oil (E.O) was investigated via GC-MS technique. In rat model, rosemary was administrated orally (in diet) for two months. Lipid profile, antioxidant biomarkers, kidney functions and histopathological examinations were assessed.

Results: Hesperidin (4878.88?ppm) and ellagic acid (403.57?ppm) are among the major phenolic and flavonoid constituents in rosemary powder. Camphor (18.36%) and α-pinene (12.74%) represent the main E.O active ingredients. Rats treated with rosemary E.O showed a significant elevation in serum HDL (28.28%) accompanied by a decrease in LDL (115.47%). A significant decrease in serum creatinine and urea was also reported (69.72 and 109.89%, respectively). Moreover, serum glutathione peroxidise (GSH-Px) activity has been significantly increased. Kidney histopathological examinations confirmed the protective effect against DEN-induced abnormalities.

Conclusion: Rosemary (powder/E.O) was able to reduce or even prevent the severity of diethylnitrosamine-induced renal dysfunction.     

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats

The widespread use of sodium nitrite (NaNO₂) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO ₂ is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO ₂-induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO ₂ at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO ₂ induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO ₂-treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO ₂-induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.     

Conductive polymer-based bioelectrochemical assembly for in vitro cytotoxicity evaluation: Renoprotective assessment of Salvia officinalis against carbon tetrachloride induced nephrotoxicity

BackgroundThe rise of organic electronics represents one of the most prominent technological developments of the last two decades, with its interface with biological systems highlighting new directions of research. The “soft” nature of conducting polymers renders them unique platforms for cell-based microdevices, allowing their implementation in drug discovery, pharmaceutical effect analysis, environmental pollutant testing etc.MethodsCellular adhesion, proliferation and viability experiments were carried out to verify the biocompatibility of a PEDOT conductive polymer surface. Cyclic voltammetry was employed for estimating the electrocatalytic activity of the renal cell/electrode interface. The nephrotoxicity agent CCl₄ and the medicinal plant Salvia officinalis were used on the proposed assembly. Renal cell viability was also assayed through the MTT assay.ResultsRenal cells were able to adhere and proliferate on the conducting polymer surface. Electrochemical responses of the polymer exhibited good correlation with cell number and CCl₄ concentration. Amelioration of the CCl₄-induced renotoxicity by co-incubation with Salvia officinalis extract was demonstrated by both the MTT assay and the electrode's capacitance.ConclusionsA conducting polymer-based bioelectrochemical assembly was established for in vitro mammalian cytotoxicity/cytoprotection assessment, employing renal cell monolayers as the primary transducers for signal generation and biological sensing.General significanceThe knowledge on PEDOT mammalian cell biocompatibility and possible applications was expanded. The proposed interdisciplinary approach connects soft electronics with biology and could provide a useful tool for preliminary crude drug screening and bioactivity studies of natural products or plant extracts in vitro.     

Grapefruit Derived Flavonoid Naringin Improves Ketoacidosis and Lipid Peroxidation in Type 1 Diabetes Rat Model

BackgroundHypoglycemic effects of grapefruit juice are well known but the effects of naringin, its main flavonoid on glucose intolerance and metabolic complications in type 1 diabetes are not known.ObjectivesTo investigate the effects of naringin on glucose intolerance, oxidative stress and ketonemia in type 1 diabetic rats.MethodsSprague-Dawley rats divided into 5 groups (n = 7) were orally treated daily with 3.0 ml/kg body weight (BW)/day of distilled water (group 1) or 50 mg/kg BW of naringin (groups 2 and 4, respectively). Groups 3, 4 and 5 were given a single intra-peritoneal injection of 60 mg/kg BW of streptozotocin to induce diabetes. Group 3 was further treated with subcutaneous insulin (4.0 IU/kg BW) twice daily, respectively.ResultsStretozotocin (STZ) only-treated groups exhibited hyperglycemia, polydipsia, polyuria, weight loss, glucose intolerance, low fasting plasma insulin and reduced hepatic glycogen content compared to the control group. Furthermore they had significantly elevated Malondialdehyde (MDA), acetoacetate, β-hydroxybutyrate, anion gap and significantly reduced blood pH and plasma bicarbonate compared to the control group. Naringin treatment significantly improved Fasting Plasma Insulin (FPI), hepatic glycogen content, malondialdehyde, β-hydroxybutyrate, acetoacetate, bicarbonate, blood pH and anion gap but not Fasting Blood Glucose (FBG) compared to the STZ only-treated group.ConclusionsNaringin is not hypoglycemic but ameliorates ketoacidosis and oxidative stress. Naringin supplements could therefore mitigate complications of diabetic ketoacidosis.     

Monoterpene synthesis in shoots regenerated from callus cultures

-Shoots regenerated from two-year old callus cultures of Lavandula angustifolia and Rosmarinus officinalis accumulated monoterpenes characteristic of the parent tissue. No such compounds could be detected in undifferentiated callus maintained under a variety of conditions.     

Modulatory role of Emblica officinalis fruit extract against arsenic induced oxidative stress in Swiss albino mice

Arsenic, an important human toxin, is naturally occurring in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of the world, particularly Asia. Epidemiological studies have shown a strong association between chronic arsenic exposure and various adverse health effects, including cardiovascular diseases, neurological defects and cancer of lung, skin, bladder, liver and kidney. The protective role of the fruits of Emblica officinalis (500 mg/kg b.wt.) was studied in adult Swiss albino mice against arsenic induced hepatopathy. Arsenic treated group (NaAsO₂, 4 mg/kg b.wt.) had a significant increase in serum transaminases and lipid peroxidation (LPO) content in liver, whereas significant decrease was recorded in hepatic superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) and serum alkaline phosphatase activity. Combined treatment of Emblica and arsenic (pre and post) declined the serum transaminases and LPO content in liver whereas significant increase was noticed in SOD, CAT, GST and serum alkaline phosphatase activities. Liver histopathology showed that Emblica fruit extract had reduced karyolysis, karyorrhexis, necrosis and cytoplasmic vacuolization induced by NaAsO₂ intoxication. Thus it can be concluded that pre- and post-supplementation of E. officinalis fruit extract significantly reduced arsenic induced oxidative stress in liver.     

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.