Moringa oleifera leaves ethanolic extract influences DNA damage signaling pathways to protect liver tissue from cobalt -triggered apoptosis in rats.

This study assessed the potential of Moringa oleifera leaves ethanol extract (MLEE) in attenuating the detrimental effects of cobalt dichloride (CoCl2) on rat liver. Forty rats were assigned to five equal groups: control group, MLEE-treated group, CoCl2-treated group, prophylaxis co-treated group, and therapeutic co-treated group. The levels of Co, hepatic injury markers, total antioxidant capacity (TAC), and oxidative stress biomarkers (reactive oxygen species [ROS] and protein carbonyl [PC]) were evaluated. Comet assay was used to evaluate the extent of DNA damage. Further, the expression profile of DNA-damage effector genes was assayed by real-time quantitative polymerase chain reaction (qRT-PCR) analysis. Immunohistochemical analysis of heat shock protein (HSP-70) in hepatocytes was conducted. The results showed that the exposure of CoCl2 to rats resulted in declined TAC, elevated oxidative injury, and induced DNA damage markers. Upregulation of mRNA expression of tumor suppressor protein (P53), apoptosis inducing factor (AIF), and apoptotic peptidase activating factor 1 (Apaf-1) was observed. The immunostaining density of HSP-70 expression was found to be elevated. Thus, MLEE reduced the CoCl2-induced genotoxicity by preventing CoCl2-induced generation of ROS, and protected against ROS mediated-oxidative injury and DNA damage. Moreover, the expression of DNA damage effector genes was affected. Based on these results, we conclude that MLEE is more effective when administered as a prophylactic regimen with the exposure to CoCl2.

Apitoxin alleviates methyl mercury-induced peripheral neurotoxicity in male rats by regulating dorsal root ganglia neuronal degeneration and oxidative stress.

Methylmercury (MeHg) toxicity is associated with extensive neuronal degeneration of dorsal root ganglia (DRG). This study aimed to assess the ameliorative effect of bee venom (BV) on methyl mercury chloride (MeHgCl)-induced peripheral neurotoxicity using DRGs in rats. Forty-eight adult male Sprague Dawley rats were allocated into four equal groups: G I: control (gavaged MilliQ water 1 ml/rat), G II: subcutaneously injected with BV (0.5 mg/kg b.wt), G III: gavaged MeHgCl (6.7 mg/kg b.wt), and G IV: received MeHgCl+BV. Dosing was done five times/week for 2 weeks. Ataxic behavior and visual impairments were significantly increased, whereas the movement behavior and motility gait were suppressed in the MeHgCl group. MeHgCl significantly decreased total antioxidant capacity (TAC) in DRG and significantly decreased the serum levels of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß) levels were significantly elevated, whereas interleukin 10 (IL-10) levels were significantly decreased in the MeHgCl group compared with the control group. DRGs of the MeHgCl-exposed rats showed pyknotic shrunken neurons with perineural vacuolations, demyelination of nerve axons, and proliferation of the satellite cells. MeHgCl significantly induced a higher positive index ratio of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin immunostaining in the DRG. BV administration significantly mitigated the MeHgCl-induced alterations in oxidative stress-related indices. BV modified the immunostaining of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin-positive index ratio in the DRG of the MeHgCl group. Our findings acknowledged that BV could enhance in vivo neuroprotective effects against MeHgCl-induced DRGs damage in male rats.

Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes.

BACKGROUND/AIMS: Melamine (ML) is a common food adulterant and contaminant. Moringa oleifera is a well-known medicinal plant with many beneficial biological properties. This study investigated the possible prophylactic and therapeutic activity of an ethanolic extract of M. oleifera (MEE) against ML-induced hepatorenal damage. METHOD: Fifty male Sprague Dawley rats were orally administered distilled water, MEE (800 mg/kg bw), ML (700 mg/kg bw), MEE/ML (prophylactically) or MEE+ML (therapeutically). Hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP) in serum were measured. Serum total bilirubin, direct bilirubin, indirect bilirubin, protein, albumin, and globulin contents were also assayed, and urea and creatinine levels were determined. Moreover, antioxidant enzyme activity of glutathione peroxidase (GPx) and catalase (CAT) in serum levels were quantified. Complementary histological and histochemical evaluation of renal and hepatic tissues was conducted, and expression of oxidative stress (GPx and CAT) and apoptosis-related genes, p53 and Bcl-2, in hepatic tissue were assessed. In parallel, transcriptional expression of inflammation and renal injury-related genes, including kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), and tumor necrosis factor alpha (TNF-α) in the kidney tissue were determined. RESULTS: ML caused significant increases in serum levels of ALT, AST, ALP, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine. Further, ML treated rats showed significant reductions in serum levels of protein, albumin, globulin, GPx, and CAT. Distinct histopathological damage and disturbances in glycogen and DNA content in hepatic and renal tissues of ML treated rats were observed. KIM-1, TIMP-1, and TNF-α gene expression was significantly upregulated in kidney tissue. Also, GPx, CAT, and Bcl-2 genes were significantly downregulated, and p53 was significantly upregulated in liver tissue after ML treatment. MEE significantly counteracted the ML-induced hepatorenal damage primarily for co-exposed rats. CONCLUSION: MEE could be an effective therapeutic supplement for treatment of ML-induced hepato-renal damage, probably via modulating oxidative stress, apoptosis, and inflammation.

The efficiency of pomegranate (Punica granatum) peel ethanolic extract in attenuating the vancomycin-triggered liver and kidney tissues injury in rats.

This study evaluated the potential of Punica granatum peel ethanol extract (PPEE) in attenuating the liver and kidney tissue injury induced by vancomycin (VM) treatment in rats. Fifty rats were distributed equally into five groups: control group, PPEE-administered group (100 mg/kg BW/day for 2 weeks; orally), VM-treated group (443.6 mg/kg BW, every alternate day for 2 weeks; intraperitoneally), pre-treated group, and concomitant-treated group. The biochemical response and the histopathology of the hepatic and renal tissue of the treated animals were assessed. The results showed that VM treatment induced substantial hepatotoxicity and nephrotoxicity, evidenced by a significant elevation in tissue injury and lipid oxidative (malondialdehyde) and inflammatory response (C-reactive protein) biomarkers, with lowered antioxidants and protein levels. Additionally, VM treatment induced various morphological, cytotoxic, vascular, and inflammatory perturbations as well as upregulation in the immune-expression of Caspase-3 and downregulation of BCL-2. Moreover, PPEE co-treatment was found to reduce the VM-induced toxicity by protecting the tissue against reactive oxygen species (ROS)-mediated oxidative damage, and inflammation as well as hinder the apoptotic cell death by modulating the expression of apoptosis-related proteins. Thus, we conclude that the PPEE administration showed more restoring efficacy when administered prior to VM medication.

Extra virgin olive oil enhances the hepatic antioxidant defense and inhibits cytogenotoxic effects evoked by 5-hydroxymethylfurfural in mice.

This study was performed to assess the ability of the food genotoxicant 5-hydroxymethylfurfural (5-HMF) to induce DNA damage and oxidative injuries in the liver of mice as a possible mechanism of toxic action and to evaluate the role of extra virgin olive oil (EVOO) in inhibiting these injuries. For this purpose, 80 mice were assigned into four equal groups of 20 mice each. Group 1 was kept as control and group 2 was given 5-HMF (250 mg/kg bw) by intraperitoneal (IP) injection 3 times weekly for 4 weeks. Group 3 received EVOO (300 µl/kg bw) orally daily for 4 weeks. Group 4 was co-treated with both 5-HMF (250 mg/kg bw) with IP injection and EVOO (300 µl/kg bw) orally 3 times weekly for 4 weeks. IP injection of 5-HMF resulted in a significant decrease in albumin, globulin, and total protein contents and significant increases in alanine transaminase, aspartate transaminase, and alkaline phosphatase activities. Administration of EVOO alone or with 5-HMF reduced the 5-HMF-induced alterations and restored the liver function biomarkers, antioxidant defense system, and histoarchitecture of the liver to normal values. EVOO also inhibited the genotoxic and apoptotic effects of 5-HMF suggesting that EVOO could provide liver protection through its powerful antioxidant and confirm its good nutriceutical and pharmacological properties.

Protective effect of Pleurotus cornucopiae mushroom extract on carbon tetrachloride-induced hepatotoxicity.

Pleurotus cornucopiae (PC) mushrooms are found in the field and commonly known in Japan as Tamogidake mushrooms. The present study investigated the protective effects of an aqueous extract of PC on carbon tetrachloride (CCl4)-induced hepatotoxicity and the possible mechanism involved in this protection including cytochrome P450 (CYP) 2E1. Wistar rats were pretreated with aqueous extracts of PC (0, 100, 200, and 400 mg/kg) orally for 8 days prior to the intraperitoneal administration of a single dose of CCl4 (0.5 ml/kg) or corn oil. Pretreatment with PC mushroom extract significantly prevented the increased serum enzyme activities of alanine and aspartate aminotransferases in a dose-dependent manner, and suppressed the expression of CYP2E1. PC mushroom extract also protected hepatocytes from the damage effects of CCl4 as remarked by histological and electromicroscopical findings. It was concluded that repeated daily doses of aqueous extracts of PC mushroom reduced the toxic effects exerted by CCl4 on the liver.

The impacts of individual and combined exposure to cadmium and lead on intraocular pressure, electroretinography, and residual changes in the rabbit eyes.

The human eye is very vulnerable to various environmental pollutants. Cadmium (Cd) and lead (Pb) are widely spread heavy metals. The goal of the existing study is to explore the impact of single or joint exposure to Cd and Pb on the eye indicators. In this study, male New Zealand white rabbits were treated orally for 30 days with Cd (5 mg Cd Cl2/kg bw) associated or not with Pb (12.5 mg lead acetate/kg bw). Fundus and slit lamp examinations, electroretinography (ERG), intraocular pressure (IOP), Cd and Pb residues, and the histopathological picture of the eye were studied. The results revealed that the oral dosing of Cd or Pb evoked a significant (p < 0.05) decline in a- and b-wave amplitudes, under scotopic conditions, and IOP values. Single Pb or Cd treatment showed a significant (p < 0.001) increase in their residues in the whole eye tissue of the Pb- or Cd-treated group. Eye structures of Cd- or Pb-intoxicated rabbit showed mild degenerated changes of cornea and sclera tissues with the presence of irregular variably sized eosinophilic droplets in the lens. Notably, the simultaneous exposure to Cd and Pb leads to an antagonistic outcome in all of the estimated parameters. These findings concluded that oral exposure to Cd or Pb could significantly disturb the vision but their joint exposure caused an opposing effect on nearly all of these disturbances.

Palliative effects of Moringa olifera ethanolic extract on hemato-immunologic impacts of melamine in rats.

Melamine (MEL) is a widespread food contaminant and adulterant. Moringa olifera is a widely known medicinal plant with various pharmacological properties. Herein, this study aimed to investigate, for the first time, the probable protective or therapeutic role of M. olifera ethanolic extract (MOE) against MEL induced hemato-immune toxic hazards. Fifty Sprague Dawely male rats were orally treated with distilled water, MOE (800 mg/kg bw), MEL (700 mg/kg bw), MOE/MEl or MOE + MEl. Erythrogram and leukogram profiling were evaluated to assess hematological status. Innate immune functions were evaluated via measuring lysozyme levels, nitric oxide concentration, and bactericidal activity of phagocytes. Serum immunoglobulin levels were estimated as indicators of humoral immunity. Histologic and immunohistochemical evaluations of splenic tissues were also performed. The results indicated that MEL caused a significant decline in RBC, Hb, PCV, total WBC, neutrophil, lymphocyte, phagocytes bactericidal activity, lysozyme activity, nitric oxide, total IgM and IgG levels. Also, MEL induced various pathologic lesions in the spleen with strong expression of CD4 and CD8 positive cells. MOE significantly counteracted the former anaemic, leucopenic, innate and humoral depressant effects of MEL particularly at co-exposure. In conclusion, these findings revealed that MOE could be candidate therapy against MEL hemato-immunotoxic impacts.

Antigenotoxic effect of Pleurotus cornucopiae extracts on the mutagenesis of Salmonella typhimurium TA98 elicited by benzo[a]pyrene and oxidative DNA lesions in V79 hamster lung cells.

Pleurotus cornucopiae (PC) mushroom with a brilliant yellow pileus is found in the field and known in Japan as Tamogi dake mushroom. The purpose of this paper is to investigate the mechanism of the antimutagenic effect of PC mushroom using both the Ames test and Comet assay. We have found a strong inhibitory effect of both aqueous and organic PC extracts on the mutagenicity elicited by benzo[a]pyrene (B[a]P). This inhibition was dose-dependent in reaction mixtures containing cytosolic and microsomal fractions (S-9) from untreated rat liver as well as in those containing S-9 from aryl hydrocarbon receptor (Ah) ligand of Sudan III-treated rats. Sudan III was a potent inducer of cytochrome P450 1A (CYP1A) activity. We treated rats with Sudan III to enhance the metabolic activation of B[a]P by the S-9 fraction. To explain whether this antimutagenicity was due to the inhibition of CYP1A activity that metabolically activates B[a]P, we tested the effects of the extracts on activities of CYP1A1 and CYP1A2, represented by ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD), respectively. Both aqueous and organic extracts inhibited EROD activity at all dose levels, while the inhibitory effect was only observed at high doses with regard to MROD activity. Furthermore, pre-treatment of Chinese hamster V79cells with PC extracts significantly reduced H2O2-induced-DNA damage, indicating that PC extracts provide a protective effect against oxidative DNA damage. These results indicate that whole-mushroom extracts contain compounds that may inhibit the metabolic activation of B[a]P by CYP1A1 as well as prevent oxidative DNA damage.