Mechanisms of Action of Diallyl Disulfide Against Trichloromethane-Induced Renal Toxicity is Via Inhibitions of Oxidative Stress, NFkB Activation, and Apoptosis in Rats

The renal-protective effect of diallyl disulfide (DADS) on tricholoromethane (CHCl3)-induced renal toxicity was investigated. Twenty five rats, divided into five groups of five animals each were used. CHCl3 at the dose of 200 mg/kg was orally administered, and concomitantly treated with DADS (50 mg/kg), 5 days/week for a period of 3 weeks. Compared with control, there was no significant increase in kidney malondialdehyde (MDA), but a significant increase in levels of nuclear factor kappa B (NFkB) expressions, TUNEL positive cells (apoptosis), as well as hydrogen peroxide (H2O2), nitric oxide (NO) and reduced glutathione (GSH) concentrations. In addition, a significant decrease in expressions of kidney p53 and catalase (CAT) activity, and a non-significant decrease in glutathione peroxidase (GPx) activity were recorded following CHCl3 administration.  Conversely, following DADS treatment, there was a significant increase in the expressions of p53, and a significant and non-significant decrease in apoptotic positive cells and NFkB expressions respectively. Administration of DADS significantly reduced the levels of H2O2 and NO, but did not have effect on the level of GSH, while CAT and GPx activities were significant improved. Protection by DADS against TCM-induced renal-toxicity may therefore be via suppressions of NFkB activation, oxidative stress and apoptosis in rats. Keywords: Apoptosis, Diallyl disulfide, NFkB, Oxidative stress, p53, Trichloromethan

Brain, lung, and heart oxidative stress assessment of an over-the- counter pyrethroid insecticide product in Nigeria

We evaluated the brain, lung, and heart oxidative stress in rats exposed to aerosol of an over-thecounter pyrethroid insecticide product in Nigeria. The experimental animals were randomly divided into four groups: group I (control) was not exposed to the insecticide aerosol, while groups II, III, and IV were exposed to 6.0 mL m-3, 12.0 mL m-3, and 18 mL m-3 of insecticide aerosol respectively. Exposures were carried out in wooden-glass chambers one hour daily for six weeks. Malondialdehyde (MDA) and  reduced glutathione (GSH) concentrations, as well as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and  glutathione S-transferase (GST) activities were determined. The brain, lung, and heart showed no significant difference in their weights and relative weights compared with the control. A significant increase in brain lipid peroxidation (LPO) was seen in groups III and IV, while there was no significant increase in lung and heart LPO compared with control. Significant decrease in the brain and lung GSH were observed in all the treatment groups when compared with the control, but only group IV showed significant reduction in heart GSH. Also, activities of lung GST and SOD were decreased compared with control, while the activity of GPx in the lung was significantly increased in group III. Lastly, nonsignificant increase in lung CAT activity was recorded in groups II and III, but decreased in group IV compared with control. Prolonged and incessant exposure to the insecticide aerosol over a long period of time may lead to tissue oxidative stress. These findings suggest that the use of insecticide aerosol for domestic purposes should be regulated.Keywords: Insecticide aerosol, pyrethroid, oxidative stress, lipid peroxidation, rats

Brain, lung, and heart oxidative stress assessment of an over-the-counter pyrethroid insecticide product in Nigeria

We evaluated the brain, lung, and heart oxidative stress in rats exposed to aerosol of an over-the-counter pyrethroid insecticide product in Nigeria. The experimental animals were randomly divided into four groups: group I (control) was not exposed to the insecticide aerosol, while groups II, III, and IV were exposed to 6.0 mL m-3, 12.0 mL m-3, and 18 mL m-3 of insecticide aerosol respectively. Exposures were carried out in wooden-glass chambers one hour daily for six weeks. Malondialdehyde (MDA) and reduced glutathione (GSH) concentrations, as well as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) activities were determined. The brain, lung, and heart showed no significant difference in their weights and relative weights compared with the control. A significant increase in brain lipid peroxidation (LPO) was seen in groups III and IV, while there was no significant increase in lung and heart LPO compared with control. Significant decrease in the brain and lung GSH were observed in all the treatment groups when compared with the control, but only group IV showed significant reduction in heart GSH. Also, activities of lung GST and SOD were decreased compared with control, while the activity of GPx in the lung was significantly increased in group III. Lastly, non-significant increase in lung CAT activity was recorded in groups II and III, but decreased in group IV compared with control. Prolonged and incessant exposure to the insecticide aerosol over a long period of time may lead to tissue oxidative stress. These findings suggest that the use of insecticide aerosol for domestic purposes should be regulated

Ethanolic extract of Jatropha gossypifolia exacerbates Potassium Bromate-induced clastogenicity, hepatotoxicity, and lipid peroxidation in rats

Extracts of J. gossypifolia L. have been reported to have several medicinal values, including potential anti-cancer and anti-inflammatory properties. In this study, we investigated the anti-clastogenic and hepatoprotective, effects of the ethanolic leaf extract of J. gossypifolia L. in potassium bromate (KBrO3)-induced toxicity in rats. The general trend of the results indicates significant increases (p < 0.05) in mean values when toxicant (KBrO3) only group is compared with normal control group, except for catalase where a significant decrease (p < 0.05) was recorded. Surprisingly, treatment of the toxic effects of KBrO3 by J. gossypifolia did not lower the mean values of any of these parameters investigated. Instead, there were significant increases (p < 0.05) in the mean number of bone marrow micronucleated polychromatic erythrocytes (mPCEs), plasma malondialdehyde (MDA) concentration, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase activities, and sodium, while the increases in mean concentrations of creatinine, urea, and potassium were not significant (p > 0.05). Also, there was a further reduction in the activity of catalase by J. gossypifolia treatment, and was also not significant (p > 0.05). We therefore concluded that the ethanolic leaf extract of J. gossypifolia may not have a protective role against chromosomal and liver damage in KBrO3-induced toxicity, but complicating effects.Keywords: Jatropha gossypifolia, KBrO3, ethanolic extract, toxicity, rat

Ethanolic extract of Jatropha gossypifolia exacerbates Potassium Bromate-induced clastogenicity, hepatotoxicity, and lipid peroxidation in rats

Extracts of J. gossypifolia L. have been reported to have several medicinal values, including potential anti-cancer and anti-inflammatory properties. In this study, we investigated the anti-clastogenic and hepatoprotective, effects of the ethanolic leaf extract of J. gossypifolia L. in potassium bromate (KBrO3)-induced toxicity in rats. The general trend of the results indicates significant increases (p < 0.05) in mean values when toxicant (KBrO3) only group is compared with normal control group, except for catalase where a significant decrease (p < 0.05) was recorded. Surprisingly, treatment of the toxic effects of KBrO3 by J. gossypifolia did not lower the mean values of any of these parameters investigated. Instead, there were significant increases (p < 0.05) in the mean number of bone marrow micronucleated polychromatic erythrocytes (mPCEs), plasma malondialdehyde (MDA) concentration, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma glutamyl transferase activities, and sodium, while the increases in mean concentrations of creatinine, urea, and potassium were not significant (p > 0.05). Also, there was a further reduction in the activity of catalase by J. gossypifolia treatment, and was also not significant (p > 0.05). We therefore concluded that the ethanolic leaf extract of J. gossypifolia may not have a protective role against chromosomal and liver damage in KBrO3-induced toxicity, but complicating effects

Syringic acid demonstrates an anti-inflammatory effect via modulation of the NF-κB-iNOS-COX-2 and JAK-STAT signaling pathways in methyl cellosolve-induced hepato-testicular inflammation in rats

Syringic acid (SACI) is an emerging nutraceutical and antioxidant used in modern Chinese medicine. It has potential neuroprotective, anti-hyperglycemic, and anti-angiogenic properties. Methyl cellosolve (MCEL) has been reported to induce tissue inflammation in the testis, kidney, liver, and lung. This study aimed to investigate the effect and probable mechanism of action of SACI on MCEL-induced hepatic and testicular inflammation in male rats. Compared to the control group, administration of MCEL to rats significantly increased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB in the liver and testis. Additionally, the total mRNA expressions of JAK1 (in the liver only), STAT1, and SOCS1 were significantly increased in both the liver and testis, while testicular JAK1 total mRNA levels were significantly decreased.The expression of PIAS1 protein was significantly higher in the liver and testis. Treatments with SACI at 25 (except liver iNOS), 50, and 75 mg/kg significantly decreased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB compared to the control group. Furthermore, the total mRNA expressions of JAK1 and SOCS1 in the liver were significantly reduced by all doses of SACI investigated, while the total mRNA levels of liver and testis STAT1 were significantly reduced by 25 and 50 mg/kg of SACI only. In the testis, the mRNA level of SOCS1 was significantly reduced by all doses of SACI compared to MCEL only. Additionally, SACI (at 75 mg/kg) significantly reduced PIAS1 protein expression in the liver, while in the testis, SACI at all investigated doses significantly reduced the expression of PIAS1. In conclusion, SACI demonstrated a hepatic and testicular anti-inflammatory effect by inhibiting the MCEL-induced activation of the NF-κB and JAK-STAT signaling pathways in rats

Methyl cellosolve-induced hepatic oxidative stress: The modulatory effect of syringic acid on Nrf2-Keap1-Hmox1-NQO1 signaling pathway in rats

Ethnopharmacological relevance: Syringic acid (SAC) is a phenolic compound and an antioxidant that has been identified in honey, grapes, red wine, marigold and sugar apple. Due to its potent antioxidant prowess, SAC possesses hepatoprotective, nephroprotective, neuroprotective, cardioprotective and anti-inflammatory activities. Aim of the study: Judging by these credentials, this study investigated the effect of 25, 50 and 75 mg/kg body weight of SAC on hepatotoxicity induced by 100 mg/kg body weight of methyl cellosolve (MECE) in male Wistar rats. Results: Compared with control, MECE decreased the liver relative weight, nitric oxide (NO) concentration, glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities, while liver malondialdehyde (MDA), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH associated protein 1 (Keap1), heme oxygenase 1 (Hmox1) and NAD(P)H quinone oxidoreductase 1 (NQO1) levels were significantly increased. Treatments with 25, 50 and 75 mg/kg of SAC significantly decreased the concentration of MDA, Nrf2, Keap1 (by 50 and 75 mg/kg only), mRNA expressions of Hmox1, NQO1 and increased the concentration of NO, activities of GPx, GST, SOD and CAT compared with MECE only administered rats. Conclusion: In conclusion, SAC demonstrated a strong hepatoprotective role against MECE-induced hepatic depletion of endogenous antioxidant enzymes and inhibition of MECE-induced cytosolic Nrf2 activation and antioxidant response element (ARE)-dependent genes in rats