Uloga kompleksa germanija s L-cysteinom i α-tokoferolom kao stimulatora antioksidativnog obrambenog sustava štakora izloženih gama-zračenju

This study was conducted to evaluate the potency of the newly prepared germanium L-cysteine α-tocopherol complex [germanium dichloro tetrakis (L-cysteinyl-α-tocopherol amide) dichloride] as a protective agent against γ-irradiation-induced free radicals production and liver toxicity. Male Swiss albino rats were injected intraperitoneally with the germanium complex in a concentration of 75 mg kg-1 body mass per dose, for 6 successive doses, last dose administered twenty minutes pre-exposure to a single dose of whole body γ-irradiation of 6.5 Gy. Lipid peroxidation (LPx), nitric oxide (NO), glutathione (GSH) levels, and activity of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in blood and liver, and blood total protein, cholesterol, triglyceride and α-tocopherol content were estimated as well. The results revealed that administration of germanium complex pre-irradiation resulted in significant (p < 0.001) improvement compared to the irradiated group in the level of hepatic and blood LPx. Hepatic GSH revealed a significant increase (p < 0.001), while its level showed no significant variation in blood. Also, the level of NO in blood and liver increased significantly (p < 0.001). On the other hand, pretreatment with the germanium complex normalized the activities of SOD, GPx and CAT in blood and liver when compared to the irradiated group. The study also documents a marked decrease in the blood triglyceride and cholesterol (p < 0.001); and significant increase (p < 0.001) of -tocopherol and total protein contents in blood. These biochemical changes were associated with marked improvement of histological status. Therefore, the germanium L-cysteine α-tocopherol complex may be a good candidate for ameliorating the changes induced by irradiation, which indicates the beneficial radio-protective role of this antioxidant agent.U radu je procjenjivan kompleks germanija s L-cisteinom i α-tokoferolom [germanijev diklortetrakis (L-cisteinil-α-tokoferol amid) diklorid] kao zaštitno sredstvo protiv slobodnih radikala induciranih γ-zračenjem hepatotoksičnosti. Mužjacima švicarskih albino štakora davan je intraperitonealno kompleks germanija, u 6 sukcesivnih doza po 75 mg kg-1 tjelesne mase, posljednja doza dana je dvadeset minuta prije izlaganja cijelog organizma jednokratnoj dozi γ-ozračivanja od 6,5 Gy. U krvi i jetri praćena je razina lipidne peroksidacije (LPx), dušikovog(II) oksida (NO), glutationa (GSH), aktivnost antioksidativnih enzima glutation peroksidaze (GPx), superoksid dismutaze (SOD) i katalaze (CAT), te količina ukupnih proteina u krvi, kolesterola, triglicerida i α-tokoferola. Rezultati su pokazali da je primjena germanijevog kompleksa značajno (p < 0,001) poboljšala koncentraciju jetrenih i krvnih LPx. Koncentracija GSH u jetri je značajno porasla (p < 0,001), dok se njegova razina u krvi nije značajno promijenila. Koncentracija NO u krvi i jetri značajno se smanjila (p < 0,001). S druge strane, prethodna obrada s kompleksom germanija normalizirala je aktivnost SOD, GPx i CAT u krvi i jetri u odnosu na ozračenu skupinu. Istraživanja su također pokazala značajno smanjenje triglicerida i kolesterola (p < 0,001) i značajno povećanje (p < 0,001) alfa-tokoferola i ukupnih proteina u krvi. Te biokemijske promjene su povezane s izraženim poboljšanjem histoloških promjena u odnosu na ozračenu skupinu. Opisani kompleks germanija mogao bi se kao antioksidativno sredstvo potencijalno upotrijebiti za spriječavanje promjena uzrokovanih zračenjem

Ornipural^® Mitigates Malathion-Induced Hepato-Renal Damage in Rats via Amelioration of Oxidative Stress Biomarkers, Restoration of Antioxidant Activity, and Attenuation of Inflammatory Response

The current study was instigated by investigating the ameliorative potential of Ornipural® solution against the hepato-renal toxicity of malathion. A total number of 35 male Wistar albino rats were divided equally into five groups. Group 1 served as control and received normal saline intraperitoneally. Group 2, the sham group, were administered only corn oil (vehicle of malathion) orally. Group 3 was orally intoxicated by malathion in corn oil at a dose of 135 mg/kg BW via intra-gastric gavage. Group 4 received malathion orally concomitantly with Ornipural® intraperitoneally. Group 5 was given Ornipural® solution in saline via intraperitoneal injection at a dose of (1 mL/kg BW). Animals received the treatment regime for 30 days. Histopathological examination revealed the harmful effect of malathion on hepatic and renal tissue. The results showed that malathion induced a significant decrease in body weight and marked elevation in the activity of liver enzymes, LDH, and ACP. In contrast, the activity of AchE and Paraoxonase was markedly decreased. Moreover, there was a significant increase in the serum content of bilirubin, cholesterol, and kidney injury markers. A significant elevation in malondialdehyde, nitric oxide (nitrite), and 8-hydroxy-2-deoxyguanosine was observed, along with a substantial reduction in antioxidant activity. Furthermore, malathion increased tumor necrosis factor-alpha, the upregulation of IL-1B, BAX, and IFN-β genes, and the downregulation of Nrf2, Bcl2, and HO-1 genes. Concurrent administration of Ornipural® with malathion attenuated the detrimental impact of malathion through ameliorating metabolic biomarkers, restoring antioxidant activity, reducing the inflammatory response, and improving pathologic microscopic alterations. It could be concluded that Ornipural® solution demonstrates hepatorenal defensive impacts against malathion toxicity at biochemical, antioxidants, molecular, and cellular levels

Ameliorative Impacts of Wheat Germ Oil against Ethanol-Induced Hepatic and Renal Dysfunction in Rats: Involvement of Anti-Inflammatory, Anti-Apoptotic, and Antioxidant Signaling Pathways

Wheat germ oil (WGO) is a well-known product with anti-inflammatory and antioxidant properties. The current study aimed to investigate the impacts of WGO against ethanol-induced liver and kidney dysfunction at the serum, anti-inflammatory, antioxidants and anti-apoptotic signaling pathways. Rats received saline orally as a negative control or WGO in a dose of 1.5 mL/kg (1400 mg/kg body weight orally) for 15 days. The affected group received ethanol 50% v/v 10 mL/kg (5 g/kg) body weight orally once a day for consecutive 15 days to induce hepatorenal injuries in ethanolic non-treated group. The protective group received WGO daily 1 h before ethanol administration. Serum (1.5 mL) from blood was extracted and examined for the changes in biochemical assessments in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), bilirubin, serum γ-glutamyl transpeptidase (GGT), total protein, serum albumin, butyrylcholinesterase (BChE), total cholesterol (TC), total triglyceride (TG), urea, creatinine, uric acid, potassium (K+), Beta-2 microglobulin (β2M), malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) and aspartate aminotransferase (AST). Kidney and liver homogenate was used to measure MDA, GSH and catalase activities. Quantitative real time PCR (qRT-PCR) was used to express Nrf2 and HO-1 in liver, and NF-kB and kidney injury molecule (KIM-1) in kidneys, which are correlated with oxidative stress and inflammation. Capase-3 and Bcl2 genes were examined using immunohistochemical analysis in the kidney and liver. Ethanol administration induced significant alteration in examined liver and kidney markers (AST, ALT, GGT, ALP, total proteins, urea, creatinine and uric acid). Moreover, alcohol administration decreased antioxidant activities at serum and hepatorenal tissues (GSH, catalase and SOD), while MDA was increased as a tissue degradation marker. Inflammatory cytokines, together with genes of oxidative stress markers (Nrf2 and HO-1), were all affected. At cellular levels, apoptotic marker caspase-3 was upregulated, while antiapoptotic marker B-cell lymphoma 2 (Bcl2), was down regulated using immunohistochemical analysis. Of interest, pretreatment with WGO improved the side effects induced by ethanol on hepatic, renal biomarkers and reversed its impact on serum and tissue antioxidant parameters. Nrf2/HO-1 were upregulated, while NFk-B and KIM-1 were downregulated using real time PCR. Immune reactivities of caspase-3 and Bcl2 genes were restored in the protective group. In conclusion, WGO ameliorated ethanol-induced hepatic and renal dysfunction at the biochemical, molecular and cellular levels by regulating some mechanisms that controls oxidative stress, apoptosis, inflammation and anti-apoptotic pathways

Ginseng^® Alleviates Malathion-Induced Hepatorenal Injury through Modulation of the Biochemical, Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Markers in Male Rats

This study aims to see if Ginseng® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated by malathion dissolved in corn oil orally at 135 mg/kg/day. Group 3 orally received both malathion + Panax Ginseng® (300 mg/kg/day). Group 4 was orally given Panax Ginseng® at a 300 mg/kg/day dose. Treatments were administered daily and continued for up to 30 consecutive days. Malathion’s toxic effect on both hepatic and renal tissues was revealed by a considerable loss in body weight and biochemically by a marked increase in liver enzymes, LDH, ACP, cholesterol, and functional renal markers with a marked decrease in serum TP, albumin, and TG levels with decreased AchE and Paraoxonase activity. Additionally, malondialdehydes, nitric oxide (nitrite), 8-hydroxy-2-deoxyguanosine, and TNFα with a significant drop in the antioxidant activities were reported in the malathion group. Malathion upregulated the inflammatory cytokines and apoptotic genes, while Nrf2, Bcl2, and HO-1 were downregulated. Ginseng® and malathion co-treatment reduced malathion’s harmful effects by restoring metabolic indicators, enhancing antioxidant pursuit, lowering the inflammatory reaction, and alleviating pathological alterations. So, Ginseng® may have protective effects against hepatic and renal malathion-induced toxicity on biochemical, antioxidant, molecular, and cell levels