Marginal zinc deficiency alters the heart proteome of rats

Sun, Yuwei; Chen, Jianfeng; Wang, Hongmei; Song, Xinyu; Sun, Zhaohui; Zhang, Rui; Zhong, Jiayi; Gu, Xinxin; Wang, Mengxu; Peng, Chenghai; Wang, Maoqing

doi:10.1039/d2fo03815c

Food Funct.

2023

DOI: 10.1039/d2fo03815c

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Marginal zinc deficiency alters the heart proteome of rats

Yuwei Sun

Jianfeng Chen

Hongmei Wang

et al.

Abstract: Zinc deficiency is closely related to cardiovascular diseases (CVDs), but the effects of marginal zinc deficiency (MZD) after birth on the heart are unknown. In this study, 4-week-old male rats...

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Cited by 3 publications

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Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Lockwood

2024

Biometals

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Independent trials indicate that either oral Zn2+ or metformin can separately improve COVID-19 outcomes by approximately 40%. Coordination chemistry predicts a mechanistic relationship and therapeutic synergy. Zn2+ deficit is a known risk factor for both COVID-19 and non-infectious inflammation. Most dietary Zn2+ is not absorbed. Metformin is a naked ligand that presumably increases intestinal Zn2+ bioavailability and active absorption by cation transporters known to transport metformin. Intracellular Zn2+ provides a natural buffer of many protease reactions; the variable “set point” is determined by Zn2+ regulation or availability. A Zn2+-interactive protease network is suggested here. The two viral cysteine proteases are therapeutic targets against COVID-19. Viral and many host proteases are submaximally inhibited by exchangeable cell Zn2+. Inhibition of cysteine proteases can improve COVID-19 outcomes and non-infectious inflammation. Metformin reportedly enhances the natural moderating effect of Zn2+ on bioassayed proteome degradation. Firstly, the dissociable metformin–Zn2+ complex could be actively transported by intestinal cation transporters; thereby creating artificial pathways of absorption and increased body Zn2+ content. Secondly, metformin Zn2+ coordination can create a non-natural protease inhibitor independent of cell Zn2+ content. Moderation of peptidolytic reactions by either or both mechanisms could slow (a) viral multiplication (b) viral invasion and (c) the pathogenic host inflammatory response. These combined actions could allow development of acquired immunity to clear the infection before life-threatening inflammation. Nirmatrelvir (Paxlovid®) opposes COVID-19 by selective inhibition the viral main protease by a Zn2+-independent mechanism. Pending safety evaluation, predictable synergistic benefits of metformin and Zn2+, and perhaps metformin/Zn2+/Paxlovid® co-administration should be investigated.

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Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Lockwood

2024

Biometals

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Biochemical Markers of Zinc Nutrition

Wang,

Zhang,

et al. 2024

Biol Trace Elem Res

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Diabetic cardiomyopathy – Zinc preventive and therapeutic potentials by its anti-oxidative stress and sensitizing insulin signaling pathways

Cai,

Tan,

Watson

et al. 2023

Toxicology and Applied Pharmacology

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Marginal zinc deficiency alters the heart proteome of rats

Abstract: Zinc deficiency is closely related to cardiovascular diseases (CVDs), but the effects of marginal zinc deficiency (MZD) after birth on the heart are unknown. In this study, 4-week-old male rats...

Cited by 3 publications

References 56 publications

Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent

Biochemical Markers of Zinc Nutrition

Diabetic cardiomyopathy – Zinc preventive and therapeutic potentials by its anti-oxidative stress and sensitizing insulin signaling pathways

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