Investigation of the effects of alamandin and melatonin in a monocrotalin-induced pulmonary arterial hypertension model in rats

Aim: PAH has a progressive and fatal course despite current treatments. We aimed to compare the possible protective effects of ALA, MEL, and ALAMEL combination, whose beneficial effects in cardiovascular diseases have been shown before, in PAH. Material and Method: 10-week-old male rats were randomly divided into control (n=10), MCT (n=12), ALA (n=12), MEL (n=12) and ALAMEL (n=12) groups. PAH was induced by 60 mg/kg single dose sc MCT on day 1; 50 μg/kg/day ip ALA, 10 mg/kg/day ip MEL and ALAMEL combination were administered to the ALA, MEL and ALAMEL groups (respectively) between days 1-35. Echocardiographic and invasive hemodynamic measurements were performed. Hearts and lungs were taken and morphometric, histopathological, ELISA and western blot analyzes were performed. Results: RV/LV was decreased in the ALA and ALAMEL groups compared to the MCT group. RVSP was tended to reduce and RV/LV+IVS was reduced in the MEL group. Inflammatory infiltration, TIM thickness, immunoreactivity of PCNA and α-SMA were decreased in all treatment groups. Histopathological improvement in the MEL and ALAMEL groups were higher compared to the ALA group. LOX activity was reduced in all treatment groups; especially in the MEL group. Conclusion: ALA and especially MEL reduced the development of PAH with antiinflammatory, antiproliferative and antiremodeling effects, while combination treatment did not provide additional benefit. The reduction of ECM remodeling by LOX inhibition by ALA, and especially MEL, is thought to be important in the prevention of PAH. Further studies are needed to support our results.