Sesamol protects against aluminum oxide nanoparticles-induced hepatorenal toxicity in rats via modulation of oxidative stress, inflammation, apoptosis, and DNA damage.

Aluminum oxide nanoparticles (Al2 O3 -NPs) are exceedingly used in various industrial and commercial applications, providing growing concerns about their potential adverse impacts on animals and human health. Therefore, the present study was conducted to evaluate the potential protective effect of sesamol (SML) against the induced hepatorenal toxicity of Al2 O3 -NPs. Forty male rats were randomly assigned into four groups and treated orally for 28 consecutive days. Control group received distilled water. SML group received SML (100 mg/kg bw). Al2 O3 -NPs group received Al2 O3 -NPs (100 mg/kg bw). SML + Al2 O3 -NPs group received SML 2 h prior to Al2 O3 -NPs. The results revealed that Al2 O3 -NPs significantly increased serum alanine aminotransferase and aspartate aminotransferase activities and serum urea and creatinine levels. Moreover, Al2 O3 -NPs induced a significant elevation in malondialdehyde level with significant reduction in reduced glutathione content and catalase and superoxide dismutase activities, together with a marked increase of 8-hydroxy-2-desoxyguanosine level in the hepatic and renal tissues. Also, up-regulations of glutathione-S-transferase, tumor necrosis factor-alpha, and caspase-3 mRNA gene expressions were recorded in the liver and kidneys. Additionally, Al2 O3 -NPs induced multifocal areas of necrosis in hepatic parenchyma with glomerular mesangial cell proliferation and glomerular sclerosis in kidney tissues. Conversely, concomitant treatment with sesamol mitigated Al2 O3 -induced hepatorenal toxicity evidenced by improvement of liver and kidney functions that correlated with regulation of oxidant/antioxidant status, inflammatory, and apoptotic biomarkers and reduction of DNA and tissues damages. In conclusion, sesamol could exert a promising protective role against hepatorenal toxicity of Al2 O3 -NPs, possibly via its antioxidant, anti-inflammatory and anti-apoptotic properties.

Neuroprotective effect of sesamol against aluminum nanoparticle-induced toxicity in rats.

Alumina nanoparticles (ALNPs) are widely used causing neurobehavioral impairment in intoxicated animals and humans. Sesamol (SML) emerged as a natural phytochemical with potent antioxidant and anti-inflammatory properties. However, no study has directly tested the potential of SML to protect against AlNP-induced detrimental effects on the brain. AlNPs (100 mg/kg) were orally administered to rats by gavage with or without oral sesamol (100 mg/kg) for 28 days. In AlNP-intoxicated group, the brain AChE activity was elevated. The concentrations of MDA and 8-OHdG were increased suggesting lipid peroxidation and oxidative DNA damage. GSH depletion with inhibited activities of CAT and SOD were demonstrated. Serum levels of IL-1ß and IL-6 were elevated. The expressions of GST, TNF-α, and caspase-3 genes in the brain were upregulated. Histopathologically, AlNPs induced hemorrhages, edema, neuronal necrosis, and/or apoptosis in medulla oblongata. The cerebellum showed loss of Purkinje cells, and the cerebrum showed perivascular edema, neuronal degeneration, necrosis, and neuronal apoptosis. However, concomitant administration of SML with AlNPs significantly ameliorated the toxic effects on the brain, reflecting antioxidant, anti-inflammatory, and anti-apoptotic effects of SML. Considering these results, sesamol could be a promising phytochemical with neuroprotective activity against AlNP-induced neurotoxicity.

Comparative Toxicological Effects of Biologically and Chemically Synthesized Copper Oxide Nanoparticles on Mice.

INTRODUCTION: Copper oxide nanoparticles (CuO-NPs) are widely used as feed additives for livestock and poultry and implicated in many biomedical applications; however, overload of copper NPs induces various toxicological changes and dysfunction of animal's organs. Thus, this study was designed to evaluate the comparative toxicological effects of biologically and chemically synthesized CuO-NPs on mice. METHODS: Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the sizes, shapes and functional groups of CuO-NPs. Forty-five mice were randomly allocated into three groups. Control group received distilled water. The second group was administered a single dose of biologically synthesized CuO-NPs (500 mg/kg bw) orally. The third group was administered a single dose of chemically synthesized CuO-NPs (500 mg/kg bw) orally. RESULTS: TEM revealed that biologically synthesized NPs were spherical in shape, whereas chemically synthesized NPs were spherical or elongated in shape. XRD showed that the size of biologically synthesized NPs ranged from 4.14 to 12.82 nm and that of chemically synthesized NPs ranged from 4.06 to 26.82 nm. FT-IR spectroscopy indicated that the peaks appeared between 779 cm-1 and 425 cm-1 in biologically synthesized NPs and between 858 cm-1 and 524 cm-1 in chemically synthesized NPs were for Cu-O nanostructure. Four mice died due to administration of biologically synthesized CuO-NPs. Both biologically and chemically synthesized CuO-NPs induced leukocytosis, elevated serum activities of alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine and increased P53 mRNA and caspase-3 protein expressions in hepatic tissues. Moreover, CuO-NPs induced degenerative and necrotized changes in hepatic, renal and splenic tissues. Biochemical, apoptotic and pathological changes were more serious in mice administered with biologically synthesized CuO-NPs. CONCLUSION: This study indicated that a high dose of biologically and chemically synthesized CuO-NPs induced adverse effects on hepatic, renal and splenic tissues. At the same dose level, the biologically synthesized CuO-NPs evoked more potent toxic effects than the chemically synthesized CuO-NPs.

Ginseng aqueous extract ameliorates lambda-cyhalothrin-acetamiprid insecticide mixture for hepatorenal toxicity in rats: Role of oxidative stress-mediated proinflammatory and proapoptotic protein expressions.

This study was carried out to evaluate the protective effects of Panax ginseng aqueous extract (GAE) against hepatorenal toxicity induced by lambda-cyhalothrin-acetamiprid insecticide mixture in rats. A total of 32 male albino rats were assigned into four groups. Normal control group received distilled water. Insecticide control group intoxicated with the insecticide at a dose of 2.14 mg/kg b.wt orally day after day for 45 days. GAE control group was treated with GAE at a dose 200 mg/kg b.wt orally. GAE experimental group was administered GAE 1 hour before insecticide administration. Intoxication of rats with the insecticide caused a significant increase in serum aspartate aminotransferase and alanine aminotransferase activities and urea and creatinine levels as well as malondialdehyde concentration and proteins expression of caspase-3 and induced nitric oxide synthase in hepatic and renal tissues. However, it decreased the serum levels of total protein and globulin and reduced the glutathione content and catalase activity in hepatic and renal tissues. In addition, insecticide induced histopathological alterations in both hepatic and renal tissues. In contrast, GAE modulated insecticide-induced alterations in liver and kidney functions and structures as it ameliorated the effects of insecticide on the above mentioned parameters. These results indicated that GAE was a potent antioxidant agent that could protect rats against insecticide-induced hepatorenal toxicity.

The ameliorative effects of ceftriaxone and vitamin E against cisplatin-induced nephrotoxicity.

Nephrotoxicity is a common adverse effect of treatment with cisplatin (CDDP). This study was performed to evaluate the antioxidant and nephroprotective efficacy of ceftriaxone (CTX) and vitamin E (Vit.E), alone and in combination against CDDP-induced acute renal injury. Fifty-six male albino rats were equally divided into seven groups, receiving (I) normal saline, (II) CTX (100 mg/kg, intraperitoneal [i.p] injection), (III) Vit.E (100 mg/kg orally), (IV) CDDP (5 mg/kg i.p injection), (V) CDDP plus CTX, (VI) CDDP plus Vit.E, and (VII) CDDP plus CTX in combination with Vit.E. All treatments were administered daily for 10 days except CDDP, which was given as a single dose at the sixth day of the study. Compared to normal control rats, CDDP-injected rats showed significantly (p < 0.05) higher serum levels of renal injury biomarkers (uric acid, urea, and creatinine) and tumor necrosis factor-α (TNF-α), as well as increased renal tissue concentrations of malondialdehyde, nitric oxide, and TNF-α. Moreover, CDDP administration was associated with significantly lower (p < 0.05) renal tissue levels of reduced glutathione and activities of endogenous antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and total antioxidant capacity. All these alterations were significantly ameliorated in CDDP-injected rats, receiving CTX and/or Vit.E, compared to rats receiving CDDP alone. Interestingly, the antioxidant and anti-inflammatory effects were more marked in the CTX-Vit.E combination group, compared to groups receiving either drug alone. In conclusion, CTX and Vit.E (especially in combination) could counteract the nephrotoxic effect of CDDP, probably through their antioxidant activities.

Radioprotective effect of Date syrup on radiation- induced damage in Rats.

Ionizing radiation has cytotoxic and genotoxic effects caused mainly by the oxidative damage induced by free radical release. The need for radioprotectives is increasing to protect normal tissues during radiotherapy. In the present study, we investigated the radioprotective effect of Date syrup in rats subjected to whole body radiation at 6 Gy through biochemical, molecular and histopathological analysis. Significant elevations were recorded in the activities of serum ALT, AST, ALP and LDH and in the levels of all lipid profiles parameters, while the level of HDL-C was reduced. The concentration of liver MDA was elevated with depletion of hepatic glutathione (GSH) and catalase. DNA damage was evidenced by increased DNA strand breakage and DNA-protein crosslinks. Significant elevations were observed in the expression of liver TNF-α and serum activity of matrix metalloproteinase (MMP-9). Pretreatment of rats with Date syrup ameliorated the tissue damage induced by radiation as evidenced by the improvement of liver function, antioxidant status and reduction of DNA damage. Besides, liver TNF-α expression and serum MMP-9 activity were reduced. In conclusion, Date syrup could alleviate the toxic effects of ionizing radiation and thus is useful as a radioprotective in radiotherapy regimen.

Experimental Studies on Some Immunotoxicological Aspects of Aflatoxins Containing Diet and Protective Effect of Bee Pollen Dietary Supplement.

Aflatoxins (AFs), widely distributed food-borne mycotoxins, affect quality and safety of food and cause economic losses in livestock. In this study, the protective effect of Bee Pollen (BP) against some immunotoxic hazards elucidated from eating of AFs-containing diet was investigated in Wistar rats. Rats were randomly classified intofour groups and treated for 30 days, Group 1; control negative, Group 2; Total AFs (3 mg kg(-1) basal diet), Group 3; BP (20 g kg(-1) basal diet) and Group 4; AFs+BP in basal diet. The immunoprotective effect of BP was revealed in terms of increasing (relative to levels seen in Group 2 rats that consumed the AFs diet) serum total protein and globulin levels, restored normal neutrophil (PMN)/lymphocyte ratio, increased PMN phagocytic activity and increased lymphocyte proliferative capacity. Also, the use of the BP reduced spleen H2O2 levels and increased GSH content while maintaining normal levels of NO formation. Histopathologic analysis showed thatthe AFs caused lymphocytic depletion in the spleen; however, BP induced lymphocytic hyperplasia and reduced the levels of AFs-inducible cellular exhaustion or depletion. These results provide evidence of a protective effect of BP against some immunotoxic actions induced in situ by consumption of AFs.

Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: Biochemical and histopathological studies.

Spirulina platensis (SP); a microalga with high antioxidant and anti-inflammatory activities, acts as a food supplement in human and as many animal species. Deltamethrin (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to DLM leads to hepatotoxic, nephrotoxic and neurotoxic side effects for human and many species, including birds and fish. The present study was undertaken to examine the potential hepatoprotective, nephroprotective, neuroprotective and antioxidant effects of SP against sub-acute DLM toxicity in male mice. DLM intoxicated animals revealed a significant increase in serum hepatic and renal injury biomarkers as well as TNF-α level and AChE activity. Moreover, liver, kidney and brain lipid peroxidation and oxidative stress markers were altered due to DLM toxicity. Spirulina normalized the altered serum levels of AST, ALT, APL, LDH, γ-GT, cholesterol, uric acid, urea, creatinine AChE and TNF-α. Furthermore, it reduced DLM-induced tissue lipid peroxidation, nitric oxide and oxidative stress in a dose-dependent manner. Collectively, that Spirulina supplementation could overcome DLM-induced hepatotoxicty, nephrotoxicity and neurotoxicity by abolishing oxidative tissue injuries.