Adebowale Bernard Saba

Molecular targets of [6]‐gingerol: Its potential roles in cancer chemoprevention

A wide variety of phenolic compounds derived from spices possess potent antioxidant, anti‐inflammatory, antimutagenic, and anticarcinogenic activities. [6]‐gingerol (1‐[4′‐hydroxy‐3′‐methoxyphenyl]‐5‐hydroxy‐3‐decanone) is the major pungent principle of ginger, with numerous pharmacological properties including antioxidant, anti‐inflammation, and antitumor promoting properties. It could decrease inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF‐α) expression through suppression of I‐kappaB alpha (IκBα) phosphorylation, nuclear factor kappa B (NF‐κB) nuclear translocation. Other antiproliferative mechanisms of [6]‐gingerol include the release of Cytochrome c, Caspases activation, and increase in apoptotic protease‐activating factor‐1 (Apaf‐1) as mechanism of apoptosis induction. Taken together, the chemopreventive potentials of [6]‐gingerol present a promising future alternative to therapeutic agents that are expensive, toxic, and might even be carcinogenic.

Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats

Removal of lead from the environment of man or otherwise, the movement of man from lead‐contaminated areas has been employed as a means of abatement of the toxic effects of lead. Whether toxic effects in already‐exposed individuals subside after lead withdrawal remains unanswered. To understand the reversibility of nephrotoxicity induced by lead acetate, male Wistar rats were orally exposed to 0.25, 0.5, and 1.0 mg/mL of lead acetate for 6 weeks. Activities of glutathione‐s‐transferase, catalase (CAT), superoxide dismutase (SOD) and the concentrations of hydrogen peroxide (H2O2), and malondialdehyde increased significantly (p < 0.05) in a dose‐dependent manner, whereas reduced glutathione (GSH) level and glutathione peroxidase activity were significantly reduced. The pattern of alterations in most of the oxidative stress and antioxidant parameters remained similar in rats from the withdrawal period, although CAT and SOD activities reduced, in contrast to their elevation during the exposure period. Serum creatinine levels were significantly elevated in both exposure and withdrawal experiments whereas serum blood urea nitrogen levels were not significantly different from the control in both exposure and withdrawal periods. The histological damage observed include multifocal areas of inflammation, disseminated tubular necrosis, and fatty infiltration of the kidney tubules both at exposure and withdrawal periods. The results suggest that lead acetate‐induced nephrotoxicity by induction of oxidative stress and disruption of antioxidant. The aforementioned alterations were not reversed in the rats left to recover within the time course of study.

Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in Wistar rats.

Lead acetate (PbA) is one of the major environmental contaminants with grave toxicological consequences both in the developing and developed countries. The liver and erythrocyte antioxidant status and markers of oxidative were assessed. Exposure of rats to PbA led to significant decline (p < 0.05) in hepatic and erythrocyte glutathione peroxidase (GPx), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) content. Similarly, malondialdehyde (MDA) and H(2)O(2) concentrations were significantly (p < 0.05) elevated. Histopathology and immunohistology of liver of rats exposed to PbA showed focal areas of necrosis and COX-2 expression after 6 weeks of PbA withdrawal. Taken together, hepatic and erythrocytes antioxidant defence system failed to recover after withdrawal of the exposed PbA for the period of the study. In conclusion, experimental animals exposed to PbA did not recover from hepatotoxicity and disruption of erythrocyte antioxidant defence system via free radical generation and oxidative stress.

Cyclophosphamide-induced hepatotoxicity in wistar rats: The modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical

Background: Gallic acid (GA) is an endogenous plant phenol known to have antioxidant, free radical scavenging ability, anti-inflammatory, anti-cancer, and anti-fungal properties. The aim of this study was to assess the protective effect of GA on cyclophosphamide (CPA)-induced hepatotoxicity in male Wistar rats. Methods: Sixty rats were grouped into six groups of 10 rats per group. Group 1 received distilled water. Group 2 received CPA at 200 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 received a single dose of CPA (200 mg/kg) intraperitoneally on day 1 and then were treated with GA at 60 and 120 mg/kg body weight for 14 days, respectively. Rats in Groups 5 and 6 only received GA at 60 and 120 mg/kg body weight for 14 days, respectively. GA was administered orally. Results: CPA induced hepatic damage as indicated by significant elevation (P < 0.05) in aspartate aminotransferase, organ weight, and evidence by the histological study. CPA also induced hepatic oxidative stress as indicated by significant elevation (P < 0.05) in malondialdehyde content, hydrogen peroxide (H2O2) generation, nitrite level, and the level of glutathione (GSH) peroxidase crashed in the CPA-treated group. GA enhanced the antioxidant defense system as indicated by significant elevation (P < 0.05) in GSH level, catalase activity, and GSH-S-transferase activity. Conclusions: Taken together, the result of this present study shows that GA has a protective effect on CPA-induced hepatotoxicity.

Hepatoprotective and in vivo antioxidant activities of ethanolic extract of whole fruit of Lagenaria breviflora

Abstract Background: This study was designed to investigate the hepatoprotective and in vivo antioxidant effects of the ethanol extract of whole fruit of Lagenaria breviflora (LB) in experimental animals. Methods: Forty nine Wistar albino rats were divided into seven groups of seven. Group I served as the control group; rats in Group II were given i.p. carbon tetrachloride (CCL4) (1.5 mL/kg) alone; Groups III–VI received different concentrations of plant extract (100, 250 and 500 mg/kg) with CCL4 and Group VII received kolaviron (KV) at 200 mg/kg as a reference hepatoprotective agent. Results: There was a significant (p<0.05) increase in malondialdehyde (MDA) and hydrogen peroxide (H202) generation in the serum of CCL4 treated rats (Group II) while the serum glutathione (GSH) level decreased significantly. Pretreatment with LB extract led to a significant (p<0.05) increase in serum GSH and a significant (p<0.05) reduction in MDA and H2O2generation. The activities of marker enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin, creatinine and blood urea nitrogen (BUN) increased (p<0.05) significantly in CCL4 treated rats (Group II). Conclusions: The present study suggested that treatment with LB extract enhances the recovery from CCL4 induced hepatic damage and oxidative stress via its antioxidant and hepatoprotective properties.

Gallic Acid Ameliorates Cyclophosphamide-Induced Neurotoxicity in Wistar Rats Through Free Radical Scavenging Activity and Improvement in Antioxidant Defense System

ABSTRACT Cyclophosphamide (CPA) is a widely used anticancer chemotherapeutic agent and its toxicity has been associated with its toxic metabolites phosphormide mustard. Therefore, the ameliorative effect of Gallic acid against neurotoxicity was examined in this study. Sixty rats were grouped into 10 rats per group. Group 1 received saline orally. Group 2 received CPA at 100 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 were treated with Gallic acid (GA) at 60 and 120 mg/kg body weight only for 10 days and also received a single dose of CPA (100 mg/kg) intraperitoneally on day 1, respectively. Rats in groups 5 and 6 received GA at 60 and 120 mg/kg body weight only for 10 days. Groups 3, 4, 5, and 6 received GA orally. The cerebellar and cerebral malondialdehyde (MDA) contents and hydrogen peroxide generation were significantly (p < .05) elevated. The cerebellar and cerebral catalase (CAT), superoxide dismutase and glutathione-S-transferase (GST) activities were significantly (p < .05) reduced in CPA treated group. The activity of glutathione peroxidase (GPx) was significantly increased in rats that were treatment with CPA. Also, nitrite content was significantly elevated in the brain of rats that received the toxic dose of CPA. All these findings suggest that treatment with GA (60 and 120 mg/kg) ameliorated the neurotoxicity induced by CPA via reduction of oxidative stress and increase in antioxidant defense system. Combining all, chemotherapeutic agents with structure/function similar to GA could be of potential benefit to the pharmaceutical industries as an adjuvant in chemotherapy with little or no side effects.

Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats

The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg−1 for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg−1 on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg−1) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg−1 for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione‐S‐transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA‐treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.

Lipoproteins and Cardiovascular Diseases

Lipids consists of a broad group of naturally occurring molecules that include fats, waxes, sterols including cholesterol, fat-soluble vitamins (such as vitamins A, D, E, and K), monoglycerides, diglycerides, triglycerides, phospholipids, and others. Lipids were previously known as sources of energy storage and the building blocks for cell membrane. Lipids are now known to play several key roles in intracellular signalling, membrane trafficking, hormonal regulation, blood clotting (Muller-Roeber and Pical, 2002; Vance and Vance, 2002; Fahy et al., 2009). All lipids may be defined as hydrophobic or amphiphilic small molecules. The amphiphilic nature of some lipids allows them to form structures such as vesicles, liposomes, or membranes in an aqueous environment. Biological lipids originate entirely or in part from two distinct types of biochemical subunits, which are ketoacyl and isoprene groups (Fahy et al., 2009).

Biochemical and electrocardiographic studies on the beneficial effects of gallic acid in cyclophosphamide-induced cardiorenal dysfunction

Abstract Background Cardiac toxicity is one of the life-threatening complications of cancer therapy. Cyclophosphamide (CYP) is an alkylating agent with potent antineoplastic and immunosuppressive properties and possibly the most widely used antineoplastic agent. Chronic cardiotoxicity associated with CYP is characterized by progressive heart failure developing from weeks to years after therapy. Methods In this study, rats were administered with (60 mg/kg and 120 mg/kg) alone or in combination with single intraperitoneal (200 mg/kg) administration of CYP for 7 days. CYP was only administered on day 1. Results The administration of CYP led to a significant (p<0.05) increase in cardiac and renal malondialdehyde (MDA) contents and hydrogen peroxide (H2O2) generation. Also, the activities of catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) levels were significantly (p<0.05) reduced following CYP treatment. A significant (p<0.05) increase in serum myeloperoxidase (MPO) activity was recorded in rats administered CYP only. Electrocardiogram (ECG) showed a significant (p<0.05) increase in heart rate (HR) accompanied by transient decrease in QRS duration. Histologic examination revealed architectural anarchy of both heart and kidney of rats that received only CYP. Conclusions In this study, treatment with gallic acid (60 mg/kg and 120 mg/kg) restored the enzymic and non-enzymic antioxidants and also attenuated cardiotoxic and nephrotoxic effect of CYP through free radical scavenging activity, anti-inflammatory and improvement of antioxidant defence system.

Anti-inflammatory and analgesic properties of the ethanolic extract of Cnidoscolus aconitifolius in rats and mice.

Abstract Background: Ethanolic leaf extract of Cnidoscolus aconitifolius was evaluated for analgesic and anti-inflammatory activities. Methods: The analgesic activity of the extract was assayed by the formalin-induced paw licking test, acetic acid-induced abdominal writhing and hot plate test, whereas its anti-inflammatory activity was determined by its effects on carrageenan-induced paw edema. Results: The extract of C. aconitifolius prolonged the reaction time of mice to pain in a dose-dependent manner. The optimal analgesic effect of the extract was obtained when the extract was administered 90 min before pain stimulation in the hot plate test. The extract of C. aconitifolius (100 or 200 mg/kg b.w.) inhibited acetic acid-induced irritation of paws of rats comparably with that of indomethacin (10 mg/kg b.w.) and had significantly lower mean number of lickings of paws than the control rats (p<0.05). Carrageenan-induced edema was markedly inhibited (p<0.05) by the extracts (100 and 200 mg/kg b.w.) when compared with control rats. Inhibition of writhing movement in rats administered with the extract was lower (p<0.05) than rats administered with indomethacin but its effect was dose-dependent. Conclusions: Our investigations show that C. aconitifolius possesses significant anti-inflammatory and analgesic activities that should be explored.