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Introduction Curcumin is an inducer of heme oxygenase enzyme-1 (HO-1) that is involved in erectile signaling via elevating cyclic guanosine monophosphate (cGMP)levels. Aim To assess the effect of oral administration of a water-soluble long-acting curcumin derivative on erectile signaling. Methods Two hundred and thirty six male white albino rats were divided into four groups; group 1 (N = 20) includes control. Group 2 (N = 72) was equally divided into four subgroups; subgroup 1 received pure curcumin (10 mg/kg), subgroup 2 received the long-acting curcumin derivative (2 mg/kg), subgroup 3 received the long-acting curcumin derivative (10 mg/kg), and subgroup 4 received sildenafil (4 mg/kg). Subgroups were sacrificed after the first, second, and third hour. Group 3 (N = 72) was equally divided into the same four subgroups already mentioned and were sacrificed after 24 hours, 48 hours, and 1 week. Group 4 (N = 72) was subjected to intracavernosal pressure (ICP) measurements 1 hour following oral administration of the same previous doses in the same rat subgroups. Main Outcome Measure Cavernous tissue HO enzyme activity, cGMP, and ICP. Results In group 2, there was a significant progressive maintained elevation of HO activity and cGMP tissue levels starting from the first hour in subgroups 3 and 4, whereas, the rise in HO activity and cGMP started from second hour regarding the other rat subgroups. Sildenafil effect decreased after 3 hours. In group 3, there was a significant maintained elevation of HO activity and cGMP tissue levels extended to 1 week as compared to controls for all rat subgroups that received both forms of curcumin. In group 4, long-acting curcumin derivative exhibited more significant potentiation of intracavernosal pressure as compared to control and to the pure curcumin. Conclusion Water-soluble long-acting curcumin derivative could mediate erectile function via upregulating cavernous tissue cGMP. Abdel Aziz MT, El Asmer MF, Rezq A, Kumosani TA, Mostafa S, Mostafa T, Atta H, Abdel Aziz Wassef M, Fouad HH, Rashed L, Sabry D, Hassouna AA, Senbel A, and Abdel Aziz A. Novel water-soluble curcumin derivative mediating erectile signaling

Introduction Activation of the renin‐angiotensin system which is common in diabetes mellitus might affect heme oxygenase (HO‐1) gene expression. Aim Assessment of the effects of administration of angiotensin II (Ang II) receptor antagonist (losartan) with HO‐1 inducer or inhibitor on erectile signaling in diabetic rats. Materials and Methods Seventy male rats were divided equally into seven groups; healthy controls, streptozotocin‐induced diabetic rats, rats on citrate buffer, diabetic rats on losartan, diabetic rats on HO‐1 inducer (cobalt protoporphyrin [CoPP]), diabetic rats on losartan and CoPP, and diabetic rats on losartan and HO‐1 inhibitor (stannus mesoporphyrin [SnMP]). Main Outcome Measure HO enzyme activity, HO‐1 gene expression, cyclic guanosine monophosphate (cGMP) assay, intracavernosal pressure (ICP), and cavernous tissue sinusoids surface area. Results HO‐1 gene expression, HO enzymatic activity, and cGMP were significantly decreased in the cavernous tissue of diabetic rats. These parameters were significantly elevated with the use of CoPP that restored the normal control levels of HO enzyme activity. Administration of losartan exhibited a significant enhancing effect on these parameters compared with the diabetic group, but not restored to the control levels, whereas administration of CoPP combined with losartan led to the restoration of their normal levels. ICP demonstrated significant decline in diabetic rats. The use of CoPP and/or losartan led to its significant improvement compared with diabetic rats. Administration of either losartan and/or CoPP led to a significant increase in the cavernous sinusoids surface area of diabetic rats. Administration of losartan with SnMP significantly decreased the enhancing effect of losartan on the studied parameters. Conclusion The decline in erectile function in diabetes mellitus could be attributed to the downregulation of HO‐1 gene expression. HO‐1 induction added to Ang II receptor antagonist could improve erectile function. Abdel Aziz MT, El Asmer MF, Mostafa T, Atta H, Mahfouz S, Fouad H, Rashed L, Sabry D, Hassouna A, Abdel Aziz AT, Senbel A, and Demery A. Effects of losartan, HO‐1 inducers or HO‐1 inhibitors on erectile signaling in diabetic rats.