Gossypol and hypokalaemia

Wang, Christina; Yeung, Raymond W.

doi:10.1016/0010-7824(85)90047-2

Cited by 22 publications

(6 citation statements)

References 33 publications

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“…Wang & Yeung (1985) reviewed the causes of clinical hypokalaemia and concluded that the most frequent cause is excessive loss of K through the kidneys. Although short‐term treatment with gossypol acetic acid (WHO; 0.5–4.0 mg/kg/day) did not alter renal tubular function in the dog ( van Ypersele de Strihou et al ., 1988 ), the possibility of a longer‐term renal effect was suggested.…”

Section: Hypokalaemiamentioning

confidence: 99%

“…Because no incidence of hypokalaemia was observed among a small group of Brazilian volunteers during gossypol treatment ( Coutinho & Melo, 1988), it was again suggested that the hypokalaemia was either a characteristic of Chinese men only or of some men with a particular genetic disposition. Familial hypokalaemia, predominantly affecting males and transmitted as an autosomal dominant trait, has been reported from all parts of the world and from different ethnic groups, although hypokalaemic paralysis associated with thyrotoxicosis occurs predominantly in Asian men ( Wang & Yeung, 1985). The possible aetiology of gossypol‐related hypokalaemia remained unresolved and attention was focused on its amelioration.…”

Section: Hypokalaemiamentioning

confidence: 99%

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Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug

1998

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Following clinical trials conducted in China in the 1970s, gossypol was proposed as a drug for male contraceptive use. This review summarizes the extensive investigations on formal animal toxicology and on the recovery of fertility in men after stopping gossypol treatment which led to the decision by the Special Programme of Research, Development and Research Training in Human Reproduction (HRP) at the World Health Organization (WHO), that gossypol would not be acceptable as an antifertility drug. It is concluded that the assessment of gossypol reinforces the mandatory requirement that future contraceptive drugs must be developed by the established routes of appropriate animal toxicology and phased clinical studies.

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Section: Hypokalaemiamentioning

confidence: 99%

Section: Hypokalaemiamentioning

confidence: 99%

Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug

1998

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“…The renal mechanisms by which gossypol produces hypokalemia are not well understood. Some investigators have suggested that gossypol induces renal leakage of potassium both in animals and in humans (Wang and Yeung, 1985). The most likely mechanism is a direct toxic effect of gossypol on the renal tubules.…”

Section: Poratmentioning

confidence: 99%

Effects of gossypol on the motility of mammalian sperm

Porat

1990

Molecular Reproduction Devel

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“…Besides its antifertility effects, other biological properties have also been reported [ 1 , 2 ], of which antiproliferative effects have been recently drawn considerable attention [ 3 , 4 ]. The use of gossypol as an alternative anticancer drug is limited by two main side effects, which include (a) the occurrence of hypokalaemic paralysis [ 5 ] and (b) the acceleration of eryptosis, which may trigger hemolysis and anemia [ 6 ]. The available evidence on animals and man suggests that the direct toxic effect of gossypol on the renal tubules leads to the renal leakage of potassium and results in hypokalaemic paralysis [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-omics analyses of red blood cell reveal antioxidation mechanisms associated with hemolytic toxicity of gossypol

et al. 2017

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Gossypol is an antiproliferative drug with limited use due to its hemolytic toxicity. In this study, accelerated hemolysis was observed in the cows treated with gossypol. Comparative metabolomics were used to gain responsive pathways in the red blood cell (RBC) to the treatment, which were crossly validated by parallel iTRAQ-based proteomic analysis and enzyme activity assay. We found that gossypol treatment appeared to considerably activate pentose phosphate pathway (PPP) with an increased key product of ribose-5-phosphate and the increased abundance and activity of several key enzymes such as 6-phosphogluconate dehydrogenase, flavin reductase, and ribose-phosphate pyrophesphokinase. Meanwhile, a decreased glycolysis metabolism was observed, as many input metabolites of glycolysis were reduced in the gossypol group, whereas its distal metabolites were unchanged, along with decreased abundance of triosephosphate isomerase and increased abundance of enzymes catalyzing several distal glycolytic steps. Oxidative reduction pathways were also remarkably affected as we found a decreased substrate of flavin reductase, glutathione disulfide, increased glutathione reductase activity, and increased abundance and activity of glutathione S-transferase with the increase of its catalytic product, cysteine. Our results demonstrated that glycolysis, PPP, and oxidative reduction pathways of RBC were all involved in RBC’s response to the hemolytic toxicity of gossypol.

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Gossypol and hypokalaemia

Cited by 22 publications

References 33 publications

Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug

Gossypol: reasons for its failure to be accepted as a safe, reversible male antifertility drug

Effects of gossypol on the motility of mammalian sperm

Multi-omics analyses of red blood cell reveal antioxidation mechanisms associated with hemolytic toxicity of gossypol

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