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Reduction of oxidative stress markers in the corpora cavernosa and media of penile dorsal artery in middle-aged rats treated with COMP-4

Abstract

COMP-4, a nutraceutical combination consisting of ginger rhizome, muira puama, Paullinia cupana, and l-citrulline, enhances intracellular nitric oxide (NO) production by the corporal smooth muscle cells (CSMC). This study aims to determine if the previously shown beneficial effect of COMP-4 on the histology and function of the aging penis is associated with an antioxidative effect from endogenously produced NO. Ten-month-old male rats were treated daily for 2 months with COMP-4 or vehicle at which time the corpora and penile dorsal artery (PDA) were evaluated by immunohistochemistry for (a) apoptosis (b) proliferative cell nuclear antigen, (c) heme oxygenase-1 (HO-1), (d) myeloperoxidase (MPO), and (e) nitrotyrosine (NT). CSMC were cultured and incubated with COMP-4 in order to determine intracellular oxidative stress via the GSH/GSSG ratio. In both the corpora and PDA, daily treatment with COMP-4 resulted in an increase in both smooth muscle cell proliferation and HO-1 expression as well as a decrease in MPO. There was no change in either apoptosis or NT expression. In the CSMC cell culture, treatment with COMP-4 increased the intracellular GSH/GSSG ratio. COMP-4 appears to have an antioxidant effect on the aging vascular smooth muscle cells both in the corpora and peripheral vasculature.

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Fig. 1: TUNEL assay for apoptosis detection in paraffin-embedded rat corpora cavernosa and penile dorsal artery (PDA) smooth muscle cells.
Fig. 2: Immunohistochemistry staining with cell turnover marker proliferating cell nuclear antigen (PCNA) in rat cavernosa and PDA smooth muscle cells.
Fig. 3: Immunohistochemistry staining with antioxidative marker HO-1 in corporal smooth muscle cells of rats treated with COMP-4 for 2 months vs control group.
Fig. 4: Immunohistochemistry staining with MPO, a catalyzer of ROS and surrogate marker of oxidative stress and inflammation.
Fig. 5: In vitro study showing high levels of ROS scavenger GSH in cavernosa smooth muscle cell tissue culture incubated with COMP-4.
Fig. 6: Immunohistochemistry staining with the oxidative marker NT in rat cavernosa and PDA smooth muscle cells.

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Acknowledgements

This study was funded by NIH-National Institute on Minority Health and Health Disparities (NIH/NIMHD) 5U54MD007598-06 (MGF) and a Urology Resident Training Grant from the UCLA Department of Urology (SN). Certain aspects of the study were also supported in part by the National Institute of Neurological Disorders and Stroke and the National Institute of General Medicine NINDS/NIGMS SC1NS064611 (MGF).

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Correspondence to Sabine Nguyen.

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Nguyen, S., Castellanos, K.A., Abraham, A. et al. Reduction of oxidative stress markers in the corpora cavernosa and media of penile dorsal artery in middle-aged rats treated with COMP-4. Int J Impot Res 33, 67–74 (2021). https://doi.org/10.1038/s41443-020-0233-9

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