Codeine-induced hepatic injury is via oxido-inflammatory damage and caspase-3-mediated apoptosis.

Codeine (3-methylmorphine) is a known analgesic, antitussive, and antidiarrheal drug that is often abused for recreational purposes. It is metabolized in the liver via the cytochrome P450 system and thus hypothesized to induce hepatic injury especially when misused. Thus, the present study aimed at investigating changes in liver function, hepatic enzyme biomarker, proton pumps, antioxidant status, free radicals and TNF-α levels, as well as caspase 3 activities and hepatic DNA fragmentation after 6 weeks of oral codeine administration. Twenty-one male rabbits were randomized into 3 groups (n = 7). The control group had 1 ml of normal saline, while the low-dose and high-dose codeine groups received 4 and 10 mg/kg b.w of codeine respectively daily. The codeine-treated animals had significantly lower levels of serum proteins, increased activities of hepatic enzyme biomarkers and caspase 3, raised hepatic concentrations of free radicals and TNF-α, as well as increased hepatic DNA fragmentation. Codeine treatment also led to a significant decline in hepatic weight, activities of hepatic enzymatic antioxidant, Na+-K+-ATPase and Ca2+-ATPase. These alterations were more pronounced in high-dose codeine treated animals than in the low-dose group. Histopathological study showed moderate fatty degeneration of hepatic parenchyma, infiltration of the portal tract by inflammatory cells with dense collagen fibre deposition in codeine-treated animals. The present study revealed that codeine induced liver injury and hepatic DNA damage via caspase 3-dependent signaling by suppressing hepatic antioxidant status and enhancing free radical and TNF-α generation.

An inventory of plants commonly used in the treatment of some disease conditions in Ogbomoso, South West, Nigeria.

ETHNOPHARMACOLOGICAL RELEVANCE: This study was designed to take an inventory of medicinal plants, recipes and methods commonly used traditionally to treat some cardiovascular and inflammatory diseases in five local government areas in Ogbomoso, Oyo State, Nigeria. MATERIAL AND METHODS: First-hand field survey through semi-structured questionnaire was employed in the 5 months study. RESULTS: A total of 101 plant species (medicinal plants (80.90%), spices (17.5%) and vegetables (1.53%)) belonging to 51 different families were mentioned for the treatment of various types of cardiovascular and inflammatory diseases. The survey revealed that 51.5% of the plants mentioned are used for the management of inflammatory diseases, 34.7% for the treatment of cardiovascular diseases and 11.9% of the plants are used for the treatment of both diseases. Euphorbiaceae (7.9%) are the most frequently used families of plants for the treatment of the various types of diseases mentioned, followed by Caesalpiaceae, (4.9%), Apocynoceae (4.9%) and Poaceae (4.9%). Fifty-nine recipes are usually prepared for the treatment of the six types of inflammatory diseases while twenty-three recipes are reportedly used for the treatment of the four types of cardiovascular diseases mentioned in this study. The recipes covered in the survey were mostly prepared from leaves (37.6%) and roots (23.8%) decoction or infusions. Medications are mostly administered orally with few numbers of the recipes showing side effect. CONCLUSION: The study has documented indigenous plants in Ogbomoso as a potential source for the development of new drugs for the treatment of cardiovascular and inflammatory diseases.

Ethnobotanical survey of medicinal plants used in the treatment of malaria in Ogbomoso, Southwest Nigeria.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria infection is the second largest killer disease after HIV in Nigeria. Failure of the orthodox medications due to drug adulteration, high cost of procurement of antimalarial drugs and inconvenience experienced in the use of high dosage of the new antimalarial drug combination therapy has turned the attention of the people in the world towards the use of local herbs. MATERIALS AND METHODS: An ethnobotanical survey of medicinal plants used by the indigenous people of Ogbomoso for the treatment of malaria infection was conducted. Investigations were carried out on the names of plants, their parts (leaf, stem or root) used, method of preparing herbal antimalarial remedies, likely side effect and how it is administered were recorded through the use of a structured questionnaire. RESULTS: The results of the survey revealed that 40 plant species from 32 plant families were mostly used for treating malaria infection in Ogbomoso. Twenty-three different antimalarial recipes were mentioned in the survey. The Asteraceae and Anacardinceae were the most represented plant families followed by Malvaceae, Solanaceae, Annonaceae, Poaceae, Rutaceae and Meliaceae. The leaf and the stem bark have been the most frequently used plant parts while concoction and decoction were the most common method of preparation. Treatment regimens of malaria generally included drinking, bathing and steam inhalation of the aqueous herbal preparations for 5-7 days or until symptoms of malaria disappear. About 53% of the plants mentioned in the survey had side effect. CONCLUSIONS: Hence, the need for documentation of these plants for further investigation becomes necessary.

Increased plasma manganese, partially reduced ascorbate, 1 and absence of mitochondrial oxidative stress in type 2 diabetes mellitus: implications for the superoxide uncoupling protein 2 (UCP-2) pathway.

Oxidative stress is an important component of diabetes and its complications. Manganese (Mn), the key component of the Mitochondrial antioxidant (MnSOD), plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in inhibiting of glucose-stimulated insulin secretion (GSIS). The interactions of Mn with ascorbate and other components of this pathway have not been defined in type-2 diabetes. Fifty established type 2 diabetics (30 males, 20 females) and 30 non-diabetics (controls; 18 males, 12 females) matched for age and sex were investigated. Dietary intake, particularly of micronutrients as assessed by 24-h dietary recall was similar between diabetics and controls. Weight and height of all subjects were determined and body mass index (BMI) computed after clinical assessment. Fasting plasma glucose, manganese, ascorbic acid, creatinine and K+ levels were determined; K+ was to assess the K+ channels, whereas creatinine was to assess probability of oxidative stress nephropathy. Body mass index was greater in DM than in controls (p < 0.001). Fasting plasma glucose and Mn levels (p < 0.00 and p < 0.01, respectively) were higher in diabetes than in the controls. Manganese level was greater than twice the levels in controls. Ascorbic acid was not significantly different (p > 0.05), but was 50% lower than the level in non-diabetics. Potassium like Mn and glucose was significantly higher in diabetes mellitus (DM) than in controls (p < 0.001). Creatinine was not significantly different between diabetics and controls (p > 0.05). Correlations among all parameters were not significantly different. These findings suggest absence of significant oxidative stress in the mitochondria, probably excluding a role for UCP-2-superoxide pathway in the inhibition of glucose-stimulated insulin secretion (GSIS), calling for caution in the precocious conclusion that interruption of UCP-2 activity may provide a viable strategy to improve beta-cell dysfunction in type 2 diabetes mellitus.

Protection against 2- acetyl aminofluorene-induced toxicity in mice by garlic (Allium sativum), bitter kola (Garcina kola seed) and honey.

The effects of honey (Hoc) and aqueous suspensions of garlic (Allium sativum) (Ga) and bitter kola (Garcina kola seed) (Bi) on the toxicities induced by 2-acetylaminofluorene (2-AAF) a model carcinogen, were investigated in mice. The animals were dosed for seven consecutive days with Ho, Ga and Bi as dietary supplements. They were then challenged with a single intraperitoneal (i.p.) dose of 2-AAF at 50 mg/kg bd. wt on the seventh day. The degree of clastogenicity was assessed using the mouse micronucleus assay while liver damage was monitored by measuring the level of gamma glutamyltransferase (gamma-GT) in serum and liver homogenates respectively. The results revealed that 2-AAF induced micronuclei formation in the polychromatic erythrocytes (PCEs) of the bone marrow by about five fold in comparison to the PCEs formed in control mice. Ho, Ga, and Bi also induced micronucleus formation on their own. However. feeding of any of Ho, Ga or Bi and the administration (i.p) of 2-AAF reduced significantly, the ability of 2-AAF to induce micronuclei formation in the order Ho>Ga>Bi. Furthermore, 2-AAF induced gamma-GT activity in the serum and liver homogenate by about two and a half and three folds respectively. A combination of 2-AAF and any of Ga or Bi or Ho significantly decreased 2-AAF-induced activity of gamma-GT in the order Ho>Bi>Ga (serum) and Bi>Ga=Ho (liver). These findings suggest that honey, garlic and bitter kola protect against 2-AAF-induced gamma-GTactivity and micronuleated PCEs formation.