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

GENDER-RELATED ALTERATIONS IN FREE FATTY ACIDS AND OXIDATIVE STRESS IN HYPERTENSION CO-MORBIDLY OCCURRING WITH TYPE 2 DIABETES MELLITUS

Increase in plasma free fatty acids (FFAs) concentrations may cause cellular damage via the induction of oxidative stress. The aim of this present study was to investigate FFAs and oxidative stress in hypertension co-morbidly occurring with Type 2 Diabetes Mellitus (T2DM). Age and sex matched control subjects (n=150) and patients (n=470) [hypertensive nondiabetics (HND, n=179), normotensive diabetics (ND, n=132), hypertensive diabetics (HD, n=159)] presenting at the Medical Out-Patient Clinic of the State Hospital, Abeokuta, Nigeria were recruited. Fasting plasma glucose, creatinine, urea, FFAs, thiobarbituric acid reactive substances (TBARS) were determined spectrophotometrically. The presence of either or both diseases resulted in significant increase (p<0.05) in the plasma FFAs and oxidative stress marker-TBARS in different compartments (plasma, erythrocytes andlipoproteins) for both male and female patients when compared with their control counterparts. The increase in FFAs was more marked in comorbidity female when compared with other female patients. There was significant (p<0.05) difference in gender FFAs concentrations. In both controls and patients, FFAs in plasma are significantly (p<0.05) higher in male when compared with their female counterparts. This research revealed biochemical variations in hypertension co-morbidly occurring with T2DMcharacterised by gender-related elevation in FFAs and enhanced oxidative stress. Plasma FFAs might be a good biomarker predicting the occurrence and development of hypertension and/or T2DM. &nbsp

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

Diallyl disulfide, a garlic-rich compound ameliorates trichloromethane-induced renal oxidative stress, NFkB activation and apoptosis in rats

Summary: 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

Syringic acid demonstrates better anti-apoptotic, anti-inflammatory and antioxidative effects than ascorbic acid via maintenance of the endogenous antioxidants and downregulation of pro-inflammatory and apoptotic markers in DMN-induced hepatotoxicity in rats

Dimethyl nitrosamine (DMN) is a known hepatotoxin, carcinogen, and mutagen. This study is therefore carried out to investigate the therapeutic effects of syringic acid (SYRA) and ascorbic acid (ASCA) in DMN-induced hepatic injury in rats. Following DMN administrations, malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) as well as activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were significantly increased. Also significantly increased were levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Following treatment with SYRA and ASCA, the activities of ALT, AST, GPx, CAT and SOD, as well as MDA, GSH, TNF-α, IL-1β, and NFkB levels were significantly reduced. Overall, both treatments were effective, but SYRA had a better therapeutic effect than ASCA. Therefore, this promising potential of SYRA can be taken advantage of in the treatment of DMN-induced hepatic injury

The anti-inflammatory effect of ferulic acid is via the modulation of NFκB-TNF-α-IL-6 and STAT1-PIAS1 signaling pathways in 2-methoxyethanol-induced testicular inflammation in rats

Background: Ferulic acid (FAC) is a component of plant cell walls, where it serves as a building block of lignin and pectin. As such, it is abundantly found in vegetables and other plants. In contrast, 2-methoxyethanol (2METH) is a testicular toxin commonly found in products used by humans. This study is aimed to investigate the effect of FAC on 2METH-induced testicular inflammation in rats. Method: Four groups of 5 animals each were used: Group I served as the control, Group II was exposed to 2METH only (100 mg/kg), Group III was administered 2METH (100 mg/kg) plus FAC (50 mg/kg), and Group IV served as the FAC (50 mg/kg) only group. All administrations were done orally for 30 days. Results: At the end of the study, rats administered 2METH only showed a significant increase in the testicular levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and nuclear factor κB (NF-κB), as well as RNA gene expressions of Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1), and suppressor of cytokine signaling 1 (SOCS1) compared to the control group. In contrast, treatment with FAC led to a significant decrease in the testicular levels of IL-6, TNF-α, iNOS, COX-2, NF-κB, and gene expression of STAT1, while significantly increasing the testicular gene expression of protein inhibitor of activated STAT 1 (PIAS1) compared to rats exposed to 2METH only. Conclusion: Based on the data gathered from this study, FAC demonstrated an anti-inflammatory effect by inhibiting the testicular activation of NF-κB through the downregulation of pro-inflammatory markers (IL-6, TNF-α, iNOS, and COX-2) and the inhibition of the STAT1-PIAS1 signaling pathway in rats