Dose-dependent and time-dependent metabolic, hemodynamic, and redox disturbances in dexamethasone-treated Wistar rats

Objectives Dexamethasone is used experimentally to induce insulin resistance and type 2 diabetes. However, data concerning the dose, the duration of treatment, and the associated comorbidities are inconsistent. The aim of this study was to compare the effects of different doses of dexamethasone and the duration of treatment necessary for the development of a model of insulin resistance that mimics the clinical condition with the associated comorbidities. Methods Dexamethasone was administered intramuscularly to male Wistar rats, at doses of 500 and 1,000 µg/kg/day for the subchronic treatment (eight consecutive days) and at doses of 5, 25, 50, and 100 µg/kg/day in chronic treatment (28 consecutive days). Effects on body weight, metabolism, hemodynamics, renal function, and redox status were evaluated. Results Both treatments induced a progressive body weight loss that was drastic in subchronic treatment, improved glucose tolerance without affecting fasting glycemia. Doses of 1,000 and 100 µg/kg were associated with hypertriglyceridemia, hypertension, and increased heart rate, cardiac and renal hypertrophy. Increased creatinemia associated with reduced creatinuria were observed in sub-chronic treatment while increased proteinuria and reduced creatinuria were noticed in chronic treatment. 1,000 µg/kg dexamethasone caused an increase in hepatic, and renal malondialdehyde (MDA) and glutathione (GSH) coupled with a reduction in catalase activity. The dose of 100 µg/kg induced a rise in GSH and catalase activity but reduced MDA levels in the kidney. Conclusions Doses of 1,000 µg/kg for subchronic and 100 µg/kg for chronic treatment exhibited similar effects and are the best doses to respective time frames to induce the model.

The effects of acutely and subchronically applied DL-methionine on plasma oxidative stress markers and activity of acetylcholinesterase in rat cardiac tissue

Background/Aim. Chronically induced hypermethioninemia leads to hyperhomocysteinemia which causes oxidative stress, atherogenesis, neurodegeneration and cancer. However, little is known about the acute and subchronic effects of DL-methionine (Met). The aim of study was to assess the effects of acutely and subchronically applied Met on oxidative stress parameters in rat plasma [enzymes: catalase (CAT), glutathione peroxidise (GPx), superoxide dismutase (SOD) and index of lipid peroxidation, malondialdehyde (MDA)], and acetylcholinesterase (AChE) activity in rat cardiac tissue. Methods. The enzymes activities, as well as MDA concentration were evaluated following acute (n = 8) and subchronic (n = 10) application of Met [i.p. 0.8 mmoL/kg body weight (b.w.) in a single dose in the acute overload or daily during three weeks in the subchronic overload]. The same was done in the control groups following application of physiological solution [i.p. 1 mL 0.9% NaCl (n = 8) in the acute overload and 0.1?0.2 mL 0.9% NaCl, daily during three weeks (n =10) in the subchronic overload]. Tested parameters were evaluated 60 minutes after application in acute experiments and after three weeks of treatment in subchronic experiments. Results. There were no difference in homocysteine values between the groups treated with Met for three weeks and the control group. Met administration significantly increased the activity of CAT and GPx after 1 h compared to the control group (p = 0.008 for both enzymes), whereas the activity of SOD and MDA concentrations were unchanged. Subchronically applied Met did not affect activity of antioxidant enzymes and MDA level. AChE activity did not show any change in rat cardiac tissue after 1 h, but it was significantly decreased after the subchronic treatment (p = 0.041). Conclusion. Results of present research indicate that Met differently affects estimated parameters during acute and subchronic application. In the acute treatment Met mobilizes the most part of antioxidant enzymes while during the subchronic treatment these changes seems to be lost. On the contrary, the acute Met overload was not sufficient to influence on the AChE activity, while longer duration of Met loading diminished function of the enzyme. These findings point out that methionine can interfere with antioxidant defense system and cholinergic control of the heart function.

Investigation of Aronia Melanocarpa Fruit Juice for Sedative-Hypnotic Effects in Rats

Summary Aronia melanocarpa fruit juice (AMFJ) has been intensively studied for effects on the central nervous system. The study aimed to investigate AMFJ for possible sedative-hypnotic effects in rats after acute and subchronic administration. Male Wistar rats were treated orally with three doses of AMFJ (2.5, 5.0 and 10.0 ml/kg) either once (acute treatment) or in 30 days (subchronic treatment). Control rats were similarly treated with distilled water. The tests were performed 1 hour after the last AMFJ administration. The possible sedative-hypnotic effects of the juice were investigated in the open field test (OFT) and thiopental-induced sleeping time test. Substances with sedative-hypnotic effects decrease locomotor activity in the OFT and prolong the time of thiopental-induced sleep. The results from the OFT showed that neither the acute, nor the subchronic treatment of rats with all AMFJ doses affected the horizontal and vertical locomotor activity significantly. The two patterns of administration of AMFJ (acute and subchronic) had no significant effect on the duration of thiopental-induced sleep. The lack of effect of AMFJ on locomotor activity and the lack of prolongation of thiopental-induced sleep showed that AMFJ did not display sedative-hypnotic effects in rats.

Interaction of two memory enhancing herbal drugs memory plus and mentat with morphine and imipramine in mice

Background: The non-medical self-administration of memory enhancing drugs is a common practice. Present study was designed to evaluate interactions of two such herbal drugs- Memory plus (MP) and Mentat, with other central nervous system active drugs.Methods: Two activities-analgesic activity and antidepressant activity were performed using adult albino mice of both sexes weighing 25-30g to observe the interactions of the herbal drugs with morphine and imipramine respectively. For each activity animals were divided into seven groups of six mice each. Group-I was control group receiving 0.2ml of 1% Tween 80 ip/ 0.2 ml saline p.o, Group II, III and IV acute treatment groups; received single dose of herbal (2mg/kg ip MP or 200mg/kg po Mentat) CNS active drugs alone in subeffective doses. Group II received morphine 2mg/kg ip, group III imipramine 2mg/kg ip and group IV-received MP/Mentat+ morphine or imipramine respectively. Groups V, VI and VII were subchronic treatment groups, received drugs once daily for eight days in same dose as acute treatment groups II, III and IV respectively. Analgesic activity was measured as prolongation of reaction time by hot plate method and antidepressant activity by reduction in despair time using Porsolt’s forced swimming test.Results: When administered for 8 days, both MP and Mentat potentiated the effect of morphine preventing the development of tolerance to analgesic effect (P< 0.05). However the antidepressant effect of imipramine was not modified by any in subchronic treatment groups.Conclusions: Two herbal memory enhancing preparations Memory plus and Mentat potentiate analgesic effect of morphine but not the antidepressant action of imipramine in mice.

Subchronic Treatment of Combination Extract Detam 1 Soybean and Jati Belanda Leaves has No Toxic Effect on Function, Weight, and Histopathological of Wistar Rat Kidney

The combination of Detam 1 soybean and Jati Belanda leaves proved to have effect of weight loss. Since it will become longterm using, toxicity effectvresearch is needed. This study was conducted to determine the effect of subchronic combination of ethanol extract of soybean Detam 1 (EEDS) and Jati belanda (EEJB) on kidney function, with parameters: urea and creatinine, macroscopic and histopathological of kidney. This study were conducted on 120 Wistar rats (60 males, 60 females), 90 days (treatment group) and 120 days (satellite group). Rats were divided into six treatment groups. Test results of urea and creatinine levels of all treatment groups was lower than control group (p <0.05). The treatment turned out to have a good effect on kidney function. Kidney weight of all groups showed no significant difference with the control group (p> 0.05). Histopathological score interpretation’s result of low dose group male and female kidney rats were not disturbed. In conclusion, the combination of EEDS and EEJB have a good effect on kidney function, did not lead to changes in organ weight and at low doses did not cause disturbance of renal histopathology. Key words: combination of soybean jati Belanda, subchronic treatment, kidney function, kidney’s weight, kidney’s histopathology