Key result
GGN1231 reduces proteinuria, BP, and cardiac fibrosis in rat models of chronic renal failure.
Why the study?
Drugs providing antihypertensive and protective cardiovascular actions are of clinical interest for controlling cardiovascular events and slowing the progression of kidney disease.
Does GGN1231 prevent cardiovascular damage, cardiac hypertrophy, and fibrosis in a rat model of severe chronic renal failure?
RCT
Randomized
Does GGN1231 prevent cardiovascular damage, cardiac hypertrophy, and fibrosis in a rat model of severe chronic renal failure?
The losartan-antioxidant hybrid GGN1231 attenuated cardiovascular damage, cardiac hypertrophy, and fibrosis in a rat model of severe chronic renal failure.
Findings in rat models should not change practice; leaves open translation of GGN1231 hybrids to human CKD.
Drugs providing antihypertensive and protective cardiovascular actions are of clinical interest in controlling cardiovascular events and slowing the progression of kidney disease. We studied the effect of a hybrid compound, GGN1231 (derived from losartan in which a powerful antioxidant was attached), on the prevention of cardiovascular damage, cardiac hypertrophy, and fibrosis in a rat model of severe chronic renal failure (CRF). CRF by a 7/8 nephrectomy was carried out in male Wistar rats fed with a diet rich in phosphorous (0.9%) and normal calcium (0.6%) for a period of 12 weeks until sacrifice. In week 8, rats were randomized in five groups receiving different drugs including dihydrocaffeic acid as antioxidant (Aox), losartan (Los), dihydrocaffeic acid+losartan (Aox+Los) and GGN1231 as follows: Group 1 (CRF+vehicle group), Group 2 (CRF+Aox group), Group 3 (CRF+Los group), Group 4 (CRF+Aox+Los group), and Group 5 (CRF+GGN1231 group). Group 5, the CRF+GGN1231 group, displayed reduced proteinuria, aortic TNF-α, blood pressure, LV wall thickness, diameter of the cardiomyocytes, ATR1, cardiac TNF-α and fibrosis, cardiac collagen I, and TGF-β1 expression. A non-significant 20% reduction in the mortality was also observed. This study showed the possible advantages of GGN1231, which could help in the management of cardiovascular and inflammatory processes. Further research is needed to confirm and even expand the positive aspects of this compound.
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Martínez‐Arias et al. (2023) conducted an RCT in Chronic renal failure. GGN1231 (losartan-antioxidant hybrid) vs. Vehicle, dihydrocaffeic acid (Aox), losartan (Los), and dihydrocaffeic acid+losartan (Aox+Los) was evaluated on Cardiovascular damage, cardiac hypertrophy, and fibrosis. GGN1231 reduced proteinuria, blood pressure, and cardiac fibrosis in a rat model of chronic renal failure, with a non-significant 20% reduction in mortality.
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