Browsing by Author "Rostamzadeh, Shiva"

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    Evaluation of the effect of chronic administration of pirfenidone on the tolerance to the analgesic effects of morphine in male mice
    (Tabriz University of Medical Sciences, School of Pharmacy, 2025) Rostamzadeh, Shiva; Charkhpour, Mohammad; Parvizpour, Alireza
    Introduction: The chronic use of opioids causes dependence and tolerance towards them, and various mechanisms such as oxidative stress and increased production of inflammatory factors are involved in this process; The antioxidant and anti-inflammatory effects of pirfenidone have been proven. Aim: The current study aimed to investigate the effect of chronic administration of pirfenidone on the tolerance to the analgesic effects of morphine in mice.Methods: The experiment was conducted in 6 groups of 8 mice, in first group, 8 mice were given two injections every day at interval of half an hour and each time 10 (ml/kg, i.p.) of normal saline, in second group, 10 (ml/kg) every day. kg, i.p) morphine and half an hour before that 10 (ml/kg, i.p) normal saline, in third group morphine (mg/kg, i.p 10) and half an hour before that 1 ml/kg containing pirfenidone DMSO (10%) and in other three groups, we injected three different doses of pirfenidone (25/50/100 mg/kg, i.p.) one hour before morphine. In all groups, we performed a hot plate test every other day for half an hour after the injections. Finally, blood was taken from all groups and TAC, MDA, TNF-a, IL-1, and IL-6 factors were analyzed. Results: In the group receiving vehicle and morphine on day 5 and in the groups receiving doses of 25, 50 and 100 mg/kg pirfenidone along with morphine on days 11, 11 and 3, respectively, tolerance was established, but only the dose of 25 mg/kg pirfenidone was significantly (P<0.05) delayed tolerance to morphine. Also, the level of inflammatory factor IL-6 showed a significant difference (P<0.001) only in the group receiving the pirfenidone (25 mg/kg) compared to the morphine group. Conclusion: Probably, pirfenidone (25 mg/kg) delayed the onset of tolerance to morphine due to its anti-inflammatory effects. We need more studies to understand it better.