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.

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.

Cnidoscolus aconitifolius leaf extract and ascorbate confer amelioration and protection against dimethyl nitrosamine-induced renal toxicity and testicular abnormalities in rats.

Extracts of Cnidoscolus aconitifolius (CA) have been reported to possess medicinal properties ranging from potential hepatoprotective, anti-diabetic, and anti-cardiovascular. In our previous study, gas chromatography mass spectroscopy check of CA extract showed the inclusion of 2,4-bis(1,1-dimethylethyl)-phenol, a phenolic phyto-compound that constitutes about 45 %, carotene and linoleic acid sources, and silicon-rich components. Hence we compare the preventive and ameliorative potentials of CA with ascorbate in dimethyl nitrosamine (DMN)-induced renal toxicity and sperm abnormalities in rats. Renal toxicity was investigated by quantifying the levels and activities of endogenous antioxidant parameters. Renal damage marked by significant reduction in GSH level, as well as significant elevation in MDA concentration, and activities of GPx, GST, CAT, and SOD were restored after the intervention of CA and ascorbate. Also, there was decrease in live sperm, sperm concentration, sperm gross and individual motility, and normal sperm morphology, following DMN administration. Based on the gathered results, it is concluded that ascorbate and CA demonstrate comparable ameliorative and protective effects against DMN-induced renal and testicular toxicities in rats.

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.

Thyroid and reproductive hormones disruption as well as kallikrein-3 level in dimethyl nitrosamine-induced toxicity: Effects of ascorbate treatment in male wistar rats.

Information on dimethyl nitrosamine (DMN)-induced toxicity on endocrine functions is still scanty. This study therefore investigated the outcomes of DMN-induced toxicity on endocrine (thyroid and reproductive) functions, as well as kallikrein-3 level, and effects of ascorbate treatments in male wistar rats. Thirty animals divided into six groups of five rats each were used. Group I animals were the normal control, group II animals served as vehicle control and were administered a single intraperitoneal dose of normal saline, groups III and IV were intraperitoneally injected with a single dose of 30 mg/kg DMN for 48 h, but group IV animals were post-treated orally with 5.71 mg/kg body weight (400 mg/70 kg) ascorbate for seven days, group V animals were pre-treated with same dose of ascorbate orally for seven days before intraperitoneal injection of DMN, while group VI animals were orally administered ascorbate only for seven days. Compared with control, DMN administration resulted in significant decrease (p < 0.05) in serum total cholesterol, testosterone (TST), luteinizing hormone (LH), free triiodothyronine (fT3), and kallikrein III (KLK-3) levels, as well as non-significant increase in serum thyroid stimulating hormone (TSH) level. Pre-treatment with ascorbate significantly increase LH and KLK-3 levels, while post-treatment significantly increase fT3 level. Also, pre-treatment with ascorbate significantly reduced TSH level, while there was no significant difference in TST level following ascorbate treatments. From our findings and to some extent, ascorbate demonstrates ameliorative effects against DMN-induced hormonal disruption in male wistar rats, and this may be attributed to its antioxidant property.

Amoxillin- and pefloxacin-induced cholesterogenesis and phospholipidosis in rat tissues.

BACKGROUND: To investigate whether amoxillin and pefloxacin perturb lipid metabolism. METHODS: Rats were treated with therapeutic doses of each antibiotic for 5 and 10 days respectively. Twenty four hours after the last antibiotic treatment and 5 days after antibiotic withdrawal, blood and other tissues (liver, kidney, brain, heart and spleen) were removed from the animals after an overnight fast and analysed for their lipid contents. RESULTS: Both antibiotics produced various degrees of compartment-specific dyslipidemia in the animals. While plasma and erythrocyte dyslipidemia was characterised by up-regulation of the concentrations of the major lipids (cholesterol, triglycerides, phospholipids and free fatty acids), hepatic and renal dyslipidemia was characterised by cholesterogenesis and phospholipidosis. Splenic dyslipidemia was characterised by cholesterogenesis and decreased phospholipid levels. Cardiac and brain cholesterol contents were not affected by the antibiotics. A transient phospholipidosis was observed in the brain whereas cardiac phospholipids decreased significantly. Lipoprotein abnormalities were reflected as down-regulation of HDL cholesterol. Furthermore, the two antibiotics increased the activity of hepatic HMG-CoA reductase. Although erythrocyte phospholipidosis was resolved 5 days after withdrawing the antibiotics, dyslipidemia observed in other compartments was still not reversible. CONCLUSION: Our findings suggest that induction of cholesterogenesis and phospholipidosis might represent additional adverse effects of amoxillin and pefloxacin.