Naringin corrects renal failure related to Lesch-Nyhan disease in a rat model via NOS-cAMP-PKA and BDNF/TrkB pathways.

This study explored the effect of naringin (NAR) on HGPRT1 deficiency and hyperuricemia through NOS-cAMP-PKA and BDNF/TrkB signaling pathways induced by caffeine (CAF) and KBrO3 in a rat model. Sixty-three adult male albino rats were randomly assigned into nine (n = 7) groups. Group I: control animals, Group II was treated with 100 mg/kg KBrO3 , Group III was treated with 250 mg/kg CAF, Group IV was treated with 100 mg/kg KBrO3 + 250 mg/kg CAF, Group V was administered with 100 mg/kg KBrO3 + 100 mg/kg haloperidol, Group VI was administered with 100 mg/kg KBrO3 + 50 mg/kg NAR, Group VII was administered with 500 mg/kg CAF + 50 mg/kg NAR, and Group VIII was administered with 100 mg/kg KBrO3 + 250 mg/kg CAF + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The exposure of rats to KBrO3 and CAF for 21 days induced renal dysfunction linked with Lesch-Nyhan disease. NAR obliterated renal dysfunction linked with Lesch-Nyhan disease by decreasing uric acid, renal malondialdehyde level, inhibiting the activities of arginase, and phosphodiesterase-51 (PDE-51) with corresponding upregulation of brain derived-neurotrophic factor and its receptor (BDNF-TrkB), Bcl11b, HGPRT1, and DARPP-32. Additionally, renal failure related to Lesch-Nyhan disease was remarkably corrected by NAR as shown by the reduced activities of AChE and enzymes of ATP hydrolysis (ATPase, AMPase, and ADA) with affiliated increase in the NO level. This study therefore validates NAR as nontoxic and effective chemotherapy against kidney-related Lesch-Nyhan disease by mitigating effects of toxic food additives and enzymes of ATP-hydrolysis via NOS-cAMP-PKA and BDNF/TrkB signaling pathways.

Potential Protective Effects of Naringin on Oculo-Pulmonary Injury Induced by PM10 (Wood Smoke) Exposure by Modulation of Oxidative Damage and Acetylcholine Esterase Activity in a Rat Model.

BACKGROUND: Millions of households in the world depend on wood and biomass for cooking and heating. This dependence leads to undesirable toxic effects, such as ocular and pulmonary toxicity. OBJECTIVES: The present study examined the potential oculoprotective and pulmonary protective activity of naringin (NRG), a naturally occurring flavonoid, against wood smoke (WS)-induced toxicity in a rat model. METHODS: Forty-eight adult male albino rats were randomly distributed into six (n=8) groups. All rats were fed, given water, and observed for 21 days, Group I (control) received only distilled water and no WS exposure, Group II was exposed to WS, Group III was exposed to WS and given 50 mg/kg/d α-tocopherol (vitamin E), Group IV was exposed to WS and given 80 mg/kg/day NRG, Group V was administered only 80 mg/kg/d NRG only, and Group VI was administered only 50 mg/kg/d vitamin E. WS exposure was for 20 min/d. The effect of NRG treatment on acetylcholinesterase activity, nitric oxide radical production, malondialdehyde level, and antioxidant enzymes (ie, superoxide dismustase and catalase) in WS-exposed rats was examined. RESULTS: Subchronic (21 day) exposure to WS induced ocular and pulmonary toxicity manifested by the infiltration of parenchyma, atrophy, and inflammation of the cells, which was correlated with alterations in antioxidant enzyme concentrations. Cell damage was associated with an increase in acetylcholinesterase activity and nitric oxide radical concentrations. The toxicity triggered by WS was modulated by the coadministration of NRG. CONCLUSION: These results suggest that NRG treatment may be useful to reduce WS-induced oxidative stress and related ocular and pulmonary damage in rats. (Curr Ther Res Clin Exp. 2012; 73:XXX-XXX).

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.

Exposure to leachate from municipal battery recycling site: implication as key inhibitor of steroidogenic enzymes and risk factor of prostate damage in rats.

Few or no studies have measured the effect of short- and long-term exposure to industrial leachate. Mature male Wistar strain albino rats (175-220 g) underwent sub-chronic exposure to leachate from the Elewi Odo municipal battery recycling site (EOMABRL) via oral administration for a period of 60 days at different doses (20%, 40%, 60%, 80%, and 100%) per kilogram of body weight to evaluate the toxic effects of the leachate on male reproductive function using steroidogenic enzymes and biomarkers of prostate damage. Control groups were treated equally but were given distilled water instead of the leachate. After the treatment periods, results showed that the treatment induced systemic toxicity at the doses tested by causing a significant (p<0.05) loss in absolute body weight and decline in growth rate. There was a marked significant decrease (p<0.05) in testicular activities of Δ(5)-3ß-hydroxysteroid dehydrogenase and 17ß-hydroxysteroid dehydrogenase. Conversely, the activity of prostatic acid phosphatase, a key marker enzyme for prostrate damage was significantly (p<0.05) elevated in the treated rats. Similarly, the administration of EOMABRL significantly (p<0.05) exacerbated the activity of total acid phosphatase with concomitant increase in the activity of prostatic alkaline phosphatase. These findings conclude that exposure to leachate from a battery recycling site induces sub-chronic testicular toxicity by inhibiting key steroidogenic enzymes and activating key markers linked with prostate damage/cancer in rats.

The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases.

The endothelial cells (ECs) make up the inner lining of blood vessels, acting as a barrier separating the blood and the tissues in several organs. ECs maintain endothelium integrity by controlling the constriction and relaxation of the vasculature, blood fluidity, adhesion, and migration. These actions of ECs are efficiently coordinated via an intricate signaling network connecting receptors, and a wide range of cellular macromolecules. ECs are naturally quiescent i.e.; they are not stimulated and do not proliferate. Upon infection or disease, ECs become activated, and this alteration is pivotal in the pathogenesis of a spectrum of human neurological, cardiovascular, diabetic, cancerous, and viral diseases. Considering the central position that ECs play in disease pathogenesis, therapeutic options have been targeted at improving ECs integrity, assembly, functioning, and health. The dietary intake of flavonoids present in citrus fruits has been associated with a reduced risk of endothelium dysfunction. Naringenin (NGN) and Naringin (NAR), major flavonoids in grapefruit, tomatoes, and oranges possess anti-inflammatory, antioxidant properties, and cell survival potentials, which improve the health of the vascular endothelium. In this review, we provide a comprehensive summary and present the advances in understanding of the mechanisms through which NGN and NAR modulate the biomarkers of vascular dysfunction and protect the endothelium against unresolved inflammation, oxidative stress, atherosclerosis, and angiogenesis. We also provide perspectives and suggest further studies that will help assess the efficacy of citrus flavonoids in the therapeutics of human vascular diseases.

Launaea taraxacifolia (Willd.) Amin ex C. Jeffrey inhibits oxidative damage and econucleotidase followed by increased cellular ATP in testicular cells of rats exposed to metropolitan polluted river water.

BACKGROUND: Humans are directly/indirectly exposed to hazardous chemicals from the aquatic environment. We investigated the protection of the Launea taraxacifolia methanolic extract (LTME) on the hydroxyl steroid dehydrogenases [(∆5-3ß-hydroxyl steroid dehydrogenase (∆5-3ß-HSD) and the ∆5-17ß-hydroxyl steroid dehydrogenase (∆5-17ß-HSD), testicular 5'-nucleotidase and lactate dehydrogenase (LDH)] activities as well as the key indicators of oxidative stress in germinal epithelial cells of rats induced with surulere polluted river water (SPRW). METHODS: The animals were divided into six groups (n=8). Group I was given 1 mL of distilled water only, Group II received 1 mL of SPRW only, Group III received 200 mg/kg LTME before+1 mL of SPRW after, Group IV received 200 mg/kg LTME+1 mL of SPRW, Group V received 1 mL of SPRW before+200 mg/kg LTME after and Group VI received 200 mg/kg LTME only. The treatment was done via oral administration for 28 days. RESULTS: The HPLC results showed the abundance of quercetin and quercitrin. The SPRW increased 5'-nucleotidase with the concomitant decrease of ∆5-3ß-HSD, ∆5-17ß-HSD and LDH activities in rats exposed in relation to the control. Similarly, the administration of the SPRW caused a systemic oxidative damage along with adverse histopathological changes in germinal epithelial cells. CONCLUSIONS: Interestingly, these alterations were differentially reversed by LTME via the elevation of steroidogenic enzymes and cellular ATP.

Effect of dietary supplement from mono-culture fermentation of Moringa oleifera seeds by Rhizopus stolonifer on hematology and markers linked to hypercholesterolemia in rat model.

Mono-culture fermentation by Rhizopus stolonifer could promote the healthiness of immune systems and cholesterol levels. Hence, we examined the effect of diet from mono-culture fermentation of Moringa oleifera seeds by R. stolonifer (MCF-MORS) on hematological parameters and fundamental indicators of hypercholesterolemia in rat. The animals were divided into six groups (n = 6). Group 1 was placed on basal diet. Group II, III, IV and V were placed on a basal diets supplemented with 7.5%, 15%, 22.5% and 30%, respectively, of MCF-MORS. Group VI was placed on basal diet fed with unfermented M. oleifera seeds (UF-MOS). The experiment lasted for eight weeks. The results revealed 7.5% MCF-MORS as better biological method to augment PCV, RBC and Hb count in animal model. Also, 7.5% and/or 15% MCF-MORS demonstrated highest levels in centrophils, neutrophils and eosinophils, whereas the levels of lymphocytes, basophils and monocytes showed no significant difference. Similarly, 7.5% and 15% MCF-MORS modulated LDL and HDL, respectively, better than UF-MOS; but showing no difference in cholesterol level. MCF-MORS also maintained architectural integrity of villi and splenocytes better than UF-MOS. We therefore concluded that diet from MCF-MORS at 7.5% and 15% modulates HDL, LDL, cholesterol and immune system-related disorders better than UF-MOS in rat model.

Novel therapeutic approaches of natural oil from black seeds and its underlying mechanisms against kidney dysfunctions in haloperidol-induced male rats.

BACKGROUND: Antipsychotic drugs could be nephrotoxic in schizophrenia patients. METHODS: The present study investigated the protective effect of oil from black seed on kidney dysfunctions using several biological approaches in adult rats. The animals were divided into six groups (n=10): normal control rats; haloperidol (HAL)-induced rats: induced rats were pre-, co- and post-treated with black seed oil (BSO), respectively, and the last group was treated with the oil only. The treatment was done through oral administration, and the experiment lasted 14 days. RESULTS: Therapeutic administration of HAL to rats caused reduction in both enzymatic and non-enzymatic proteins mediated by stable OH˙ and DPPH free radicals. K+, Na+ and MDA contents as well as 51 nucleotidase, aldose-reductase activities were increased with corresponding decrease in the activity of lactate dehydrogenase (LDH) in HAL-induced toxicity rats. Contrariwise, differential treatments with BSO prevented and reversed the nephrotoxicity by depleting K+, Na+, MDA contents and aldose-reductase activity, and AMP hydrolysis with increased adenosine triphosphate (ATP) in the PMFs of rat kidney. The cytotoxicity of HAL elicited on both inner renal cortex and outer medulla was equally alleviated by combined active molecules of oil from black seed (OBS). However, pre-, co- and post-treatment demonstrate significant approaches in averting nephrotoxicity of neuroleptic drug (HAL) via several biological mechanisms. CONCLUSIONS: This study therefore validates the use of black seed oil as therapy particularly for individuals with renal dysfunctions.

Neuro-Preventive Effect and Elevation of Cellular Adenosine Triphosphate by PUFAs from Pteleiosis suberosa Stem Bark on Mercury Sub-Acute Exposed Rats.

OBJECTIVES: Occupational/industrial exposure and experimental intoxication of mercury can produce neurological effects but Pteleiosis suberosa stem bark extract (PTSSBE) might be useful in the treatment of brain disorders because it's anti-ulcer, anti-inflammatory and antioxidant effects had been documented. METHODS: The present study was therefore designed to investigate some phenolic constituents, evaluate its antioxidant properties and examine its reversal effects of PTSSBE on sub-acute mercury-induced brain toxicity. Rats were divided into five groups of 10 animals each. Group I was given distilled water; group II, III, IV and V was orally administered with mercury at a dose of 3.75 mg/kg body weight. Group III, IV and V were co-treated with PTSSBE of 25, 50 and 100 mg/ kg body weight respectively, for 10 days. RESULTS: The results revealed that the stem bark extract exhibited high presence of antioxidants. Experimental exposure of rats to mercury significantly decreased the activities of catalase (CAT), lactate dehydrogenase (LDH), and the level of reduced glutathione (GSH), while the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the formation of malondialdehyde (MDA) were increased. These effects were reversed by co-administration with PTSSBE in mercury-induced brain toxicity in rats. CONCLUSION: The protective effects of Pteleiosis suberosa, during mercury exposure suggest that these phenolics and PUFAs may be helpful in treating neurological disorders and other related cerebral toxicity implicated in depleted cellular ATP and oxidative stress.

Blanching influences the phenolics composition, antioxidant activity, and inhibitory effect of Adansonia digitata leaves extract on α-amylase, α-glucosidase, and aldose reductase.

Adansonia digitata (A. digitata) leaves serve as food and has several medicinal uses in many parts of the world. This study evaluated the influence of blanching on the phenolics composition, antioxidant activity, and inhibitory effect of methanol extract of A. digitata leaves on the activities of some key enzymes (α-amylase, α-glucosidase, and aldose reductase) implicated in type 2 diabetes (T2D) in vitro. Reverse-phase HPLC analysis revealed that the leaves had appreciable levels of flavonoids and phenolic acids, including catechin, epicatechin, rutin, quercitrin, quercetin, kaempferol, and luteolin (flavonoids); gallic, chlorogenic, caffeic, and ellagic acids (phenolic acids). Blanching caused significant (P < 0.05) decrease in the flavonoids and phenolic acids contents; DPPH* (2,2 diphenyl-1-picrylhydrazyl radical) and ABTS*+ [2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation] scavenging ability; reducing power; and Fe2+-induced lipid peroxidation inhibitory capacity of the extract. Similarly, the inhibitory effect of the extract on the activities of α-amylase, α-glucosidase, and aldose reductase was significantly (P < 0.05) reduced due to blanching. Thus, A. digitata leaves extract could be effective for the management of T2D due to its flavonoids and phenolic acids content, antioxidant properties, and inhibitory potency on the activities of α-amylase, α-glucosidase, and aldose reductase. However, blanching militated against the levels of these functional attributes of the leaves and, therefore, may not be recommended for their optimal retention.

Nephritic cell damage and antioxidant status in rats exposed to leachate from battery recycling industry.

Limited studies have assessed the toxic effect of sub-acute and sub-chronic exposure of leachate (mixture of metals) in mammalian kidney. The sub-acute and sub-chronic exposure of mature male Wistar-strain albino rats (200-220 g) were given by oral administration with leachate from Elewi Odo municipal battery recycling industry (EOMABRIL) for period of 7 and 60 days respectively, at different concentrations (20%, 40%, 60%, 80% and 100%). This was to evaluate its toxic effects on male renal functions using biomarkers of oxidative stress and nephro-cellular damage. Control groups were treated equally, but given distilled water instead of the leachate. All the groups were fed with the same standard food and had free access to drinking water. Following the exposure, results showed that the treatment induced systemic toxicity at the doses tested by causing a significant (p<0.05) alteration in enzymatic antioxidants-catalase (CAT) and superoxide dismutase (SOD) in the kidneys which resulted into elevated levels of malonaldehyde (MDA). Reduced glutathione (GSH) levels were found to be significantly (p<0.05) depleted relative to the control group. Considerable renal cortical congestion and numerous tubules with protein casts were observed in the lumen of EOMABRIL-treated rats. These findings conclude that possible mechanism by which EOMABRIL at the investigated concentrations elicits nephrotoxicity could be linked to the individual, additive, synergistic or antagonistic interactions of this mixture of metals with the renal bio-molecules, alteration of kidney detoxifying enzymes and necrosis of nephritic tubular epithelial cells.

Differential protection of black-seed oil on econucleotidase, cholinesterases and aminergic catabolizing enzyme in haloperidol-induced neuronal damage of male rats.

BACKGROUND: The antipsychotic, haloperidol, is extremely efficient in the treatment of schizophrenia but its application is constrained because of irreversible adverse drug reactions. Hence, in this study, we investigate the differential effects of black seed oil on cholinesterase [acetylcholinesterase (AChE) and butrylcholinesterase (BuChE), ectonucleotidase (5'-nucleotidase), lactate dehydrogenase (LDH) and monoamine oxidase (MAO)] activities and relevant markers of oxidative stress in the cerebrum of haloperidol-induced neuronal-damaged rats. METHODS: The animals were divided into six groups (n = 10): normal control rats; haloperidol-induced rats: induced rats were pre-, co- and post-treated with black-seed oil respectively, while the last group was treated with extract oil only. The treatment was performed via oral administration and the experiment lasted 14 days. RESULTS: The results revealed an increase in 5(I) nucleotidase, a marker of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis, as well as AChE, BuChE and MAO activities, with concomitant decrease in LDH activity of cerebrum in induced rats when compared with controls. Also, administration of haloperidol caused systemic oxidative damage and adverse histopathological changes in neuronal cells, indications of mental disorder. The differential treatments with black-seed oil prevented these alterations by increasing LDH and decreasing 5(I) nucleotidase, AChE, BuChE and MAO activities in the cerebrum. Essential oil post-treatment is most efficacious in reversing haloperidol-induced neuronal damage in rat; followed by pre- and cotreatment, respectively. CONCLUSIONS: We concluded that essential black-seed oil enhanced the wellness of aminergic, purinergic and cholinergic neurotransmissions of haloperidol-induced neuronal damage in rats.

Garlic capsule and selenium-vitamins ACE combination therapy modulate key antioxidant proteins and cellular adenosine triphosphate in lisinopril-induced lung damage in rats.

BACKGROUND: Garlic capsule (GAR) and/or selenium- vitamin A, C, E (S-VACE) might be useful in the treatment of lung diseases. The present study evaluated the toxicity of lisinopril (LIS) in the lungs of male rats and the reversal effect of GAR and/or selenium-vitamins A, C, and E (S-VACE). METHODS: Group I served as the control, whereas animals in groups II, III, IV, and V received 28 mg of LIS/kg body weight by gavage. Group III was co-treated with GAR at a therapeutic dosage of 250 mg/kg body weight per day. Group IV was co-treated with S-VACE at dosage of 500 mg/kg body weight per day. Lastly, group V was co-treated with GAR and S-VACE at dosages of 250 and 500 mg/kg body weight per day, respectively. The experiment lasted for 8 days (sub-acute exposure). RESULTS: Administration of therapeutic dose of LIS to male rats depleted enzymatic antioxidants (superoxide dismutase and catalase) and cellular adenosine triphosphate content with concomitant increase in lipid peroxidation. Histopathology examination showed damage to the epithelial cells of the airways. These effects were prevented by both single and combination treatment of GAR and S-VACE in male rats with LIS-induced lung toxicity. CONCLUSIONS: We therefore concluded that the combination of GAR and S-VACE can be a novel therapy for the management of lung diseases in humans.

Effects of sub-acute methanol extract treatment of Calliandra portoricensis root bark on antioxidant defence capacity in an experimental rat model.

BACKGROUND: The attendant side effects associated with some synthetic drugs used in the management of diseases have led to the search for safer alternative therapies that are relatively cheaper with minimal side effects. METHODS: The methanol extract of Calliandra portoricensis root bark (CPRB) was orally administered at the doses of 5, 10, 20, and 25 mg/kg body weight for 14 consecutive days of 5 rats in each group. The control rats were given distilled water. RESULTS: The 95% methanol extract of CPRB significantly (p<0.05) scavenged NO• and OH• radicals compared to vitamin C. The level of lipid peroxidative products (malondialdehyde, MDA) was significantly (p<0.05) attenuated in a dose-dependent manner. Antioxidant enzymes including superoxide dismutase and catalase were significantly (p<0.05) exercabated in both liver and kidney in a dose-dependent manner. Furthermore, serum AST, alanine aminotransaminase and γ-glutamyltransferase (GGT) activity depicted non-significant (p>0.05) increase in the treated animals. The histological examination showed mild vacuolar, portal congestion and cell infiltration by mononuclear of the hepatic tissues. CONCLUSIONS: The study then concluded that a therapeutic dose of the methanol extract of CPRB triggered the antioxidant defence systems in male rats. It is, therefore, recommended that the doses should be carefully and clinically chosen because higher doses may cause some health risks.

Testicular membrane lipid damage by complex mixture of leachate from municipal battery recycling site as indication of idiopathic male infertility in rat.

Leachate from a municipal battery recycling site is a potent source of mixed-metal released into the environment. The present study investigated the degree at which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected the lipid membrane of the testes in in vitro experiment. The results showed elevated level of mixed-metals over the permissible levels in drinking water, as recommended by regulatory authorities. In the leachate samples, the levels of malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05) increased in rat testes in a dose-dependent manner. MDA induced by the municipal auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular lipid membrane capacity was compromised following treatment with leachate from the municipal battery recycling site, implicating mixed-metal exposure as the causative agent of testicular damage and male infertility.