Gossypol

Gossypol/Drug Interactions:

  • AlcoholAlcohol: There is anecdotal evidence that gossypol may inhibit alcohol dehydrogenase and aldehyde dehydrogenase, which may permit blood levels of ethanol and acetaldehyde to accumulate.
  • Androgenic agentsAndrogenic agents: Gossypol may potentiate the androgenicity of methyltestosterone (71).
  • Angiotensin converting enzyme (ACE) inhibitorsAngiotensin converting enzyme (ACE) inhibitors: ACE inhibitors may alter serum potassium levels (88). This is potentially dangerous in combination with gossypol treatment, because hypokalemia is the most commonly reported side effect of gossypol use (61; 95; 96; 97; 98; 99; 100; 101; 58; 102) and may lead to hypokalemic paralysis (105; 65; 106; 1).
  • Angiotensin converting enzyme receptor blockers (ARB)Angiotensin converting enzyme receptor blockers (ARB): Angiotensin receptor blocking agents may alter serum potassium levels (88). This is potentially dangerous in combination with gossypol treatment, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).
  • Beta-blockers (Beta adrenergic antagonists)Beta-blockers (Beta adrenergic antagonists): ( Blockers may alter serum potassium levels (88). This is potentially dangerous in combination with gossypol treatment, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).
  • ContraceptivesContraceptives: Gossypol has been found to suppress male fertility in China (131; 144; 145; 87; 2; 146; 7; 79; 80; 147; 119) and is a candidate contraceptive drug for both males and females (148; 149; 150; 151; 152; 141; 153; 154; 155; 156; 158; 159; 160; 161; 162; 163; ; 164; 157). Gossypol disrupted estrous cycles, pregnancy, and early embryo development in animal studies (64). The luteolytic effect is proposed to be the main mechanism of action for the termination of early pregnancy by gossypol, although the direct damaging effects on decidual cells and cytotrophoblasts may also play a role (74).
  • CyclosporineCyclosporine: Cyclosporine may alter serum potassium levels (88). This is potentially dangerous in combination with gossypol treatment, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).
  • Diuretics, loopDiuretics, loop: Loop diuretics may alter serum potassium levels (88). This is potentially dangerous in combination with gossypol treatment, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).
  • Fertility agentsFertility agents: Gossypol exhibited a high degree of antifertility activity in male and female animals (141; 158; 159; 160; 161; 162; 163; 164). Gossypol disrupted estrous cycles, pregnancy, and early embryo development in animal studies (64). The luteolytic effect is proposed to be the main mechanism of action for the termination of early pregnancy by gossypol, although the direct damaging effects on decidual cells and cytotrophoblasts may also play a role (74).
  • LaxativesLaxatives: According to secondary sources, overuse or misuse of stimulant laxatives with gossypol may increase the risk of potassium depletion. This is potentially dangerous, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).
  • MetyraponeMetyrapone: In in vitro study, coadministration of gossypol with metryapone decreased superoxide free-radical formation in renal microsomes (165).
  • Nonsteroidal anti-inflammatory agents (NSAIDS)Nonsteroidal anti-inflammatory agents (NSAIDS): Concomitant use with NSAIDs may increase the risk of gastrointestinal side effects associated with gossypol use (60).
  • PhenobarbitalPhenobarbital: Coadministration of gossypol with phenobarbital enhanced free-radical formation in liver microsomes in vitro (165).
  • Potassium-sparing diureticsPotassium-sparing diuretics: Potassium-sparing diuretics may alter serum potassium levels (88). This is potentially dangerous in combination with gossypol treatment, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).
  • SteroidsSteroids: Gossypol binds covalently to microsomal proteins, which may affect metabolism of steroids (72).
  • SulfadiazineSulfadiazine: Synergic effects of gossypol acetate and sulfadiazine on the lactate dehydrogenase (LDH)-X activity and viability of human sperm have been observed (139).
  • TheophyllineTheophylline: Theophylline administration may reduce the ability of gossypol to decrease sperm motility (73).

    • Gossypol/Herb/Supplement Interactions:

  • Androgenic agentsAndrogenic agents: Gossypol may potentiate the androgenicity of methyltestosterone (71).
  • AntioxidantsAntioxidants: Gossypol exhibits antioxidant action in sperm isolated from rats (8).
  • ContraceptivesContraceptives: Gossypol has been found to suppress male fertility in China (131; 144; 145; 87; 2; 146; 7; 79; 80; 147; 119) and is a candidate contraceptive drug for both males and females (148; 149; 150; 151; 152; 141; 153; 154; 155; 156; 158; 159; 160; 161; 162; 163; ; 164; 157). Gossypol disrupted estrous cycles, pregnancy, and early embryo development in animal studies (64). The luteolytic effect is proposed to be the main mechanism of action for the termination of early pregnancy by gossypol, although the direct damaging effects on decidual cells and cytotrophoblasts may also play a role (74).
  • DiureticsDiuretics: Potassium-sparing diuretics may alter serum potassium levels (88). This is potentially dangerous in combination with gossypol treatment, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).
  • Fertility agentsFertility agents: Gossypol has been found to suppress male fertility in China (131; 144; 145; 87; 2; 146; 7; 79; 80; 147; 119) and is a candidate contraceptive drug for both males and females (148; 149; 150; 151; 152; 141; 153; 154; 155; 156; 158; 159; 160; 161; 162; 163; ; 164; 157). Gossypol disrupted estrous cycles, pregnancy, and early embryo development in animal studies (64). The luteolytic effect is proposed to be the main mechanism of action for the termination of early pregnancy by gossypol, although the direct damaging effects on decidual cells and cytotrophoblasts may also play a role (74).
  • ForskolinForskolin: There is evidence that forskolin reverses gossypol's sperm antimotility effect (73).
  • LaxativesLaxatives: According to secondary sources, overuse or misuse of stimulant laxatives with gossypol may increase the risk of potassium depletion. This is potentially dangerous, because hypokalemia is the most commonly reported side effect of gossypol use and may lead to hypokalemic paralysis (61; 95; 96; 97; 98; 99; 100; 101; 58; 102; 105; 65; 106; 1).

    • Gossypol/Food Interactions:

  • Insufficient evidence.

    • Gossypol/Lab Interactions:

  • ATP levelsATP levels: In in vitro study, cells exposed to low concentrations of gossypol exhibited decreased levels of ATP (166).
  • (2-Microglobulin levels(2-Microglobulin levels: In human study, plasma and urinary (2-microglobulin levels were elevated after taking gossypol (67).
  • Blood chemistryBlood chemistry: In human studies, complete blood cell count, cholesterol, glucose, triglycerides, acid phosphatase, urea, transaminases, sodium, potassium, and peripheral blood lymphocytes were not changed significantly during gossypol treatment (70; 56; 167).
  • Blood pressureBlood pressure: In two human studies, a lack of a change was found in blood pressure following gossypol use (92; 70), although in a separate study, a trend of declining blood pressure was noted (55).
  • Body weightBody weight: In human studies, a lack of differences in terms of body weight were noted between gossypol-treated or control groups (92; 70).
  • Estradiol levelsEstradiol levels: Some human studies have shown that there is a moderate decrease in serum estradiol levels following gossypol therapy (140; 137), while another study did not detect any change (91).
  • Follicle-stimulating hormone (FSH)Follicle-stimulating hormone (FSH): In human studies, administration of gossypol caused elevation of serum FSH levels (57; 91; 137; 138; 67). Other investigators reported a lack of a change (87; 85). Several investigators observed that serum levels of FSH were correlated significantly with sperm concentrations (139; 91).
  • GonadotropinGonadotropin: In human study, gossypol supplementation altered serum gonadotropin levels (20; 139).
  • HemoglobinHemoglobin: In human study, a lack of differences in hemoglobin were found between gossypol-treated or control groups (92).
  • Luteinizing hormone (LH)Luteinizing hormone (LH): In human studies, administration of gossypol caused elevation of serum LH levels (137; 138). Other investigators reported a lack of a change (87; 85; 91). One study noted that serum LH levels that were significantly elevated during earlier phases of gossypol treatment returned to normal after cessation of treatment, except in 14 men with persistent disruption of spermatogenesis (139).
  • OvulationOvulation: Use of gossypol for more than three months was accompanied by a monophasic basal body temperature, indicating the inhibition of ovulation (93; 137). Reversibility was not tested in these studies.
  • PhospholipidsPhospholipids: A significant decrease in phospholipid levels was noted after gossypol addition to human sperm cells (168). Other studies noted a progressive decrease in the levels of phosphatidylethanolamine, phosphatidylserine, and glycerylphosphocholine with a progressive increase in the level of lysophosphatidylethanolamine following gossypol treatment (166; 169).
  • Potassium levelsPotassium levels: The most common side effect reported during gossypol use in Chinese men is hypokalemia (67; 170; 92; 133; 55). The extent of hypokalemia is related to the duration and dose of gossypol, although some studies did not find this side effect (85; 57). Potassium deficiency has been shown to enhance the antispermatogenic effect of gossypol (107).
  • Progesterone levelsProgesterone levels: Human studies have shown that there is a moderate decrease in serum progesterone levels following gossypol therapy (140; 137; 74). Gossypol alters the binding capacity of the cytosolic progesterone receptor (171).
  • ProlactinProlactin: Serum concentrations of prolactin did not change following gossypol treatment (91).
  • Serum glutamate-pyruvate transaminase (SGPT) levelsSerum glutamate-pyruvate transaminase (SGPT) levels: There is conflicting data regarding whether gossypol use may cause increased SGPT levels (133; 68).
  • TestosteroneTestosterone: Gossypol supplementation altered serum testosterone levels in some human studies (20; 139), but not in others (87; 91; 70).
  • Vitamin AVitamin A: In an animal study, rabbits that had been fed 2% cottonseed oil for seven weeks had significantly more stored hepatic vitamin A compared to rabbits fed other fats (48).
  • ZincZinc: In human study, gossypol had a lack of an effect on the seminal plasma zinc levels (90).