Hesperetin-7-O-rhamnoglucoside ameliorates dichlorvos-facilitated cardiotoxicity in rats by counteracting ionoregulatory, ion pumps, redox, and lipid homeostasis disruptions.

The contamination of edible agricultural goods with pesticides, including dichlorvos (DVDP), poses a substantial public health risk, promoting severe morbidity and mortality, especially in developing countries. It has been shown that hesperidin (hesperetin-7-O-rhamnoglucoside or Hes-7-RGlc) preserves cytomembrane, redox, and lipid homeostasis; unfortunately, its function on dichlorvos-incited heart damage has not been investigated. This work explored the ameliorative influence of Hes-7-RGlc on DVDP-activated cardiotoxicity. For this end, forty-two rats were randomly appropriated into seven groups (6 rats/group): Control, DVDP alone (8 mg.kg⁻¹day⁻¹), DVDP supplied with either Hes-7-RGlc (50 and 100 mg.kg⁻¹day⁻¹) or the reference medication atropine (0.2 mg.kg⁻¹day⁻¹), and Hes-7-RGlc alone (50 and 10 mg.kg⁻¹day⁻¹) were the seven groups investigated. DVDP was administered orally for seven days, followed by fourteen days of Hes-7-RGlc therapy. Then the rats were euthanized, and their blood and hearts were removed. Hes-7-RGlc chemotherapy substantially (p<0.05) restored DVDP-elicited dynamics in plasma and cardiac/myocardium creatine kinase isoenzyme (CK-MB), major lipids (cholesterol, triacylglycerol, and phospholipids), electrolytes (Na⁺, K⁺, Ca²âº, Mg²âº, Cl⁻), and total protein. Hes-7-RGlc remedy decidedly (p<0.05) abolished DDVP-stimulated amplification in the cardiac concentration of H2O2, NO and malondialdehyde; annulled DVDP-educed decreases in heart GSH levels, activities of GST, SOD, catalase, and glutathione peroxidase, ion transporters (Na⁺/K⁺-ATPase and Ca²âº/Mg²âº-ATPase), ALT, AST, ALP, and LDH-1. Collectively, Hes-7-RGlc can be advocated as a natural supplementary candidate and blocker of DVDP-provoked heart deficits via its capacity to reverse disruptions of electrolytes, ion pumps, redox status, and lipid homeostasis.

Ferulic acid interventions ameliorate NDEA-CCl4-induced hepatocellular carcinoma via Nrf2 and p53 upregulation and Akt/PKB-NF-κB-TNF-α pathway downregulation in male Wistar rats.

Hepatocellular carcinoma is a prevalent form of liver cancer that is life threatening. Many chemically synthesized anti-cancer drugs have various degrees of side effects. Hence, this study investigated the effect of FEAC interventions on NDEA-CCl4-induced HCAR in male Wistar rats. HCAR was induced by intraperitoneal administration of 200 mg/kg of NDEA and 0.5 mL/kg CCl4 (as a promoter of HCAR). Following the induction of HCAR, rats were treated differently with two different doses (25 and 50 mg/kg) of FEAC. HCAR induction was confirmed by the significant elevation of serum levels of ALT, AST, and α-FP. Also elevated significantly were liver levels of Akt/PKB, NF-κB, TNF-α, MDA, GSH, and activities of GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly lowered compared with normal rats. Treatment interventions with both 25 and 50 mg/kg of FEAC against the DEN-CCl4-induced HCAR gave comparable effects, marked by a significant reduction in the levels of serum ALT, AST and α-FP, as well as liver levels of MDA, GSH, Akt/PKB, NF-κB, TNF-α, GST, SOD, and CAT, while levels of liver p53 and Nrf2 were significantly elevated compared with normal rats. Put together and judging by the outcomes of this study, FEAC being a potent antioxidant may also be potent against chemical-induced HCAR via upregulation of p53 and Nrf2, as well as downregulation of the Akt/PKB-NF-κB pathway in rats.

Lycopene abolishes palmitate-mediated myocardial inflammation in female Wistar rats via modulation of lipid metabolism, NF-κB signalling pathway, and augmenting the antioxidant systems.

BACKGROUND AND AIMS: Obesity-related heart failure is exacerbated by excessive intake of saturated fats such as palmitate (PA). Lycopene (LYC) possesses anti-lipidemic, antioxidant, cytoprotective, and anti-inflammatory effects. This study, therefore, evaluated the impact of LYC against PA-invoked cardiotoxicity. METHODS AND RESULTS: Thirty-six female rats were equally divided into six groups: control; PA (5 mM); PA + LYC (24 mg/kg); PA + LYC (48 mg/kg); LYC (24 mg/kg); and LYC (48 mg/kg). The PA was administered five times weekly for seven weeks, while the LYC was given for the last two weeks. Lipids in the blood and the heart were estimated, as were oxidative stress and antioxidant indices, cardiac function, inflammation, and histology. Palmitate overload occasioned a significant (p < 0.05) increase in cardiac cholesterol (50%), phospholipids (19%), and non-esterified fatty acids (40%). However, triglyceride levels decreased (38%). Furthermore, malondialdehyde (45%), hydrogen peroxide (33%) levels and myeloperoxidase activity increased (79%). Also, cardiac gamma-glutamyl transferase (50%), serum creatine kinase activities (1.34 folds), NF-kB, interleukin1ß, and interleukin-6 mRNA expression increased in the PA group relative to the control. In contrast, reduced glutathione (13%) and nitric oxide levels (22%), interleukin-10 mRNA expression, cardiac creatine kinase (35%), lactate dehydrogenase (33%), aspartate, and alanine transaminase activities decreased markedly (15- and 10%, respectively). Also, PA caused hyperemia, congestion of the cardiac interstitium, and infiltration of inflammatory cells. However, treatment with LYC reversed the features of cardiotoxicity and histological complications caused by PA. These observations are likely because LYC has anti-inflammatory, antioxidant, and cytoprotective properties. CONCLUSION: Thus, LYC might be an appropriate remedy to manage PA-induced cardiotoxicity in female rats.

Naringin prevents cyclophosphamide-induced erythrocytotoxicity in rats by abrogating oxidative stress.

Earlier reports have shown that Cyclophosphamide (CYCP), an anti-malignant drug, elicited cytotoxicity; and that naringin has several beneficial potentials against oxidative stress and dyslipidaemias. We investigated the influence of naringin on free radical scavenging, cellular integrity, cellular ATP, antioxidants, oxidative stress, and lipid profiles in the CYCP-induced erythrocytotoxicity rat model. Rats were pretreated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) naringin before single CYCP (200 mg/kg, i.p.) administration. Afterwards, the rats were sacrificed. Naringin concentrations required for 50 % scavenging hydrogen peroxide and nitric oxide radical were 0.27 mg/mL and 0.28 mg/mL, respectively. Naringin pretreatment significantly (p < 0.05) protected erythrocytes plasma membrane architecture and integrity by abolishing CYCP-induced decrease in the activity of erythrocyte LDH (a marker of ATP). Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-induced decreases in the erythrocytes glutathione levels, activities of glutathione-S-transferase, catalase, glutathione peroxidase, and glutathione reductase; attenuated CYCP-mediated increases in erythrocytes levels of malondialdehyde, nitric oxide, and major lipids (cholesterol, triacylglycerol, phospholipids, and non-esterified fatty acids). Taken together, different acute pretreatment doses of naringin might avert CYCP-mediated erythrocytes dysfunctions via its antioxidant, free-radical scavenging, and anti-dyslipidaemia properties.

Naringin prevents cyclophosphamide-induced hepatotoxicity in rats by attenuating oxidative stress, fibrosis, and inflammation.

Cyclophosphamide (CYCP), a synthetic alkylating antineoplastic, disrupts both cancerous and non-cancerous cells to cause cancer regression and multi organotoxicity respectively. CYCP-induced hepatotoxicity is rare but possible. Evidence has shown that naringin has several beneficial potentials against oxidative stress, inflammation, and fibrosis. This study examined the chemoprotective potentials of naringin on exited radical scavenging, hepatic integrity, oxidative stress, fibrosis, and inflammation in CYCP-mediated hepatotoxicity. Rats were pre-treated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) of naringin before single CYCP (200 mg/kg, i.p.) administration. Subsequently, the rats were euthanized; blood and liver were removed, and assessed for serum and hepatic enzymes, oxidative stress, inflammation, and gene expression dynamics. Naringin concentrations required for 50% scavenging hydroxyl radical and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) radical cation were 0.32 mg/mL and 0.39 mg/mL, respectively. Pretreatment with naringin significantly (p < 0.05) abolish CYCP-induced changes in the activities of serum and hepatic ALT, AST, GGT, ALP, and LDH. Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-mediated increases in hepatic levels of malondialdehyde, hydroperoxide, and nitric oxide; reverse CYCP-induced decreases in the hepatic glutathione levels, activities of catalase, glutathione peroxidase, and glutathione reductase; and also attenuated CYCP-induced upregulation of expression of hepatic chemokine (C-C motif) ligand 2 (CCL2), interferon alpha1 (IFN-α1), interleukine-1ß, interleukine-1 receptor, and transforming growth factor beta 1 (TGF-ß1). Taken together, different doses of naringin can prevent CYCP-induced oxidants generation, hepatocytes dysfunctions, oxidative stress as well as inflammatory perturbations in rats when pre-administered for as few as 14 days.

Sub-acute exposure to Sudan IV-adulterated palm oil induces oxidative stress and represses the expression of Nrf2 and antioxidant genes in male albino rats.

This study investigated the effects of Sudan IV dye (S4D) on antioxidant biomarkers using palm oil adulterated with S4D. Thirty male albino rats were grouped into five (n = 6); Normal control, palm oil (PO), PO + S4D (100 mg/kg), PO + S4D (250 mg/kg), and S4D (250 mg/kg) for 21 days. Oxidative stress biomarkers were assessed in the serum, liver, and kidneys. Exposure to S4D (alone and in adulterated PO) occasioned significant depletions in the activities of SOD, CAT, and GPx, as well as GSH levels in the assessed compartments. Contrastingly, the levels of NO and MDA were significantly (p < 0.05) increased in the serum, liver, and kidney of rats exposed to PO + S4D (both doses) and S4D (250 mg/kg) when compared to control rats. Further, the expressions of the genes coding for CAT, GPx-1, GSR, and Nrf-2 were significantly (p < 0.05) down-regulated, relative to ß-actin, in groups exposed to S4D compared to the control. Interestingly, these parameters were not significantly different (p > 0.05) in the unadulterated PO-exposed rats compared to the control. These results show that S4D depleted the antioxidant capacities, while potentiating the generation of reactive species and oxidative damage. This study provides useful information on the oxidative mechanisms associated with consumption of S4D-containing consumer products.

Renal and testicular up-regulation of pro-inflammatory chemokines (RANTES and CCL2) and cytokines (TNF-α, IL-1ß, IL-6) following acute edible camphor administration is through activation of NF-kB in rats.

Camphor-induced oxidative stress and histopathological changes (in brain, lung, liver, kidney and testes) have been reported. We therefore investigated the effect of various doses of camphor in an acute study, on renal and testicular levels of some pro-inflammatory mediators in male wistar rats. Twenty rats divided into four groups of five rats each were used in this study. Group 1 served as control and was administered 6 mL/kg olive oil, the vehicle for camphor, while groups 2, 3 and 4 were orally administered 1000, 2000, and 4000 mg/kg body weight camphor, for seven days. Compared with control, levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß) and interleukin 6 (IL-6) were significantly increased kidney and testes by 2000 and 4000 mg/kg body weight, while interleukin 10 (IL-10) was only significantly increased by 1000 mg/kg body weight of camphor in both tissues. Also compared with control, all doses of camphor administered resulted in a significant increase in the expressions of renal and testicular nuclear factor kappa B (NFkB), cyclooxygenase 2 (COX-2), regulated upon activation normal T cell expressed and secreted (RANTES), and monocyte chemo-attractant protein 1 (MCP-1). Conclusively, use and consumption of camphor should be with caution as it could trigger renal and testicular inflammation through activation of NF-kB and up-regulation of pro-inflammatory markers.