Melatonin ameliorates low‐grade inflammation and oxidative stress in young Zucker diabetic fatty rats

The aim of this study was to investigate the effects of melatonin on low‐grade inflammation and oxidative stress in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups, each composed of 10 rats: naive (N), vehicle treated (V), and melatonin treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Pro‐inflammatory state was evaluated by plasma levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and C‐reactive protein (CRP). Also, oxidative stress was assessed by plasma lipid peroxidation (LPO), both basal and after Fe²⁺/H₂O₂ inducement. ZDF rats exhibited higher levels of IL‐6 (112.4 ± 1.5 pg/mL), TNF‐α (11.0 ± 0.1 pg/mL) and CRP (828 ± 16.0 µg/mL) compared with lean rats (IL‐6, 89.9 ± 1.0, P < 0.01; TNF‐α, 9.7 ± 0.4, P < 0.01; CRP, 508 ± 21.5, P < 0.001). Melatonin lowered IL‐6 (10%, P < 0.05), TNF‐α (10%, P < 0.05), and CRP (21%, P < 0.01). Basal and Fe²⁺/H₂O₂‐induced LPO, expressed as malondialdehyde equivalents (µmol/L), were higher in ZDF rats (basal, 3.2 ± 0.1 versus 2.5 ± 0.1 in ZL, P < 0.01; Fe²⁺/H₂O₂‐induced, 8.7 ± 0.2 versus 5.5 ± 0.3 in ZL; P < 0.001). Melatonin improved basal LPO (15%, P < 0.05) in ZDF rats, and Fe²⁺/H₂O₂‐ induced LPO in both ZL (15.2%, P < 0.01) and ZDF rats (39%, P < 0.001). These results demonstrated that oral melatonin administration ameliorates the pro‐inflammatory state and oxidative stress, which underlie the development of insulin resistance and their consequences, metabolic syndrome, diabetes, and cardiovascular disease.     

Insecticidal Activities of the Leaf Oils of Eight Cinnamomum. species Against Aedes aegypti. and Aedes albopictus.

Abstract

The leaf oils of eight Cinnamomum. species (C. rhyncophyllum. Miq., C. microphyllum. Ridl., C. pubescens. Kochummen, C. mollissimum. Hook. f., C. impressicostatum. Kosterm, C. scortechinii. Gamb., C. sintoc. Bl., and C. cordatum. Kosterm) were investigated for their larvicidal and adulticidal activities against Aedes aegypti. (Aedes aegypti Lynn) and Aedes albopictus. (Aedes albopictus Skuse). Acute mortalities of the fourth instar larvae and the adult mosquitoes were determined according to the standard WHO methods. Among the essential oils studied, the leaf oils of C. rhyncophyllum., C. microphyllum., C. pubescens., C. mollissimum., and C. impressicostatum. showed significant effects against the larvae of Ae. aegypti. and Ae. albopictus. with concentrations that caused 50% mortality (LC₅₀) values of less than 12.8 and 11.8 µg ml^?1, respectively. The essential oils that showed strong larvicidal effects also demonstrated relatively strong adulticidal effects on the mosquitoes after 3 h exposure with LC₅₀ values ranging from 133.0 to 243.0 µg ml^?1 against Ae. aegypti. and from 118.0 to 194.0 µg ml^?1 against Ae. albopictus.. The efficacy of the oils toward the larvae and adult mosquitoes of both species was nonselective as the LC₅₀ values showed little variation. The chemical composition of the oils was investigated by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). This study suggested that the essential oils containing high levels of benzyl benzoate and benzyl salicylate exhibited strong insecticidal activities against the larvae and adult mosquitoes.     

Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.     

Comparison of Aqueous Humour Concentration after Single High Dose Versus Multiple Administration of Topical Moxifloxacin in Rabbits

For the prevention of postoperative ocular infections prophylactic topical antibiotics are routinely used. Studies evaluating comparative difference between single dose versus multiple dose administration on aqueous humour concentration of moxifloxacin are lacking. This study compared the aqueous humour concentration of moxifloxacin following its topical administration in rabbit eyes with two dose regimens. Twelve albino rabbits were divided into two groups. In group-1, two drops were administered thrice (total six drops) at 2 min intervals, in both the eyes; in group-2, two drops of moxifloxacin were administered three times a day for three days and also two h before aqueous humour collection i.e. on fourth day. Mean aqueous humour concentrations were calculated and compared using Student''s ‘t’ test and P<0.05 was considered significant. Moxifloxacin concentration in aqueous humour in group-1 was 23.79 μg/ml and in group-2 was 42.08 μg/ml. Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for most bacteria. Moxifloxacin concentration in aqueous humour with multiple instillations is significantly higher than single instillation (P<0.05), which is adequate to cover ciprofloxacin-resistant gram-negative bacteria. Repeated topical moxifloxacin administration achieved significantly higher aqueous humour concentrations than single administration.