Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase and DNA integrity in rat testicular cells in vitro

Singh, Malti; Kalla, N.R.; Sanyal, Sankar Nath

doi:10.1016/j.etp.2006.06.006

Cited by 13 publications

(9 citation statements)

References 28 publications

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“…In addition, it has been shown that H2AX transcription is upregulated in T. gondii in response to oxidative DNA damage (10). Previously, Singh et al (32) demonstrated that monensin caused significant oxidative stress and DNA fragmentation in rat testicular cells. Other genes that our microarrays indicated were transcriptionally upregulated in response to monensin include that which encodes the protein phosphatase 2A (TGME49 000400), which has been shown to mediate signal transduction in DNA damage response, resulting in cell cycle arrest (24).…”

Section: Vol 55 2011mentioning

confidence: 99%

The Antibiotic Monensin Causes Cell Cycle Disruption ofToxoplasma gondiiMediated through the DNA Repair Enzyme TgMSH-1

Lavine

Arrizabalaga

2011

Antimicrob Agents Chemother

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Monensin is a polyether ionophore antibiotic that is widely used in the control of coccidia in animals. Despite its significance in veterinary medicine, little is known about its mode of action and potential mechanisms of resistance in coccidian parasites. Here we show that monensin causes accumulation of the coccidian Toxoplasma gondii at an apparent late-S-phase cell cycle checkpoint. In addition, experiments utilizing a monensinresistant T. gondii mutant show that this effect of monensin is dependent on the function of a mitochondrial homologue of the MutS DNA damage repair enzyme (TgMSH-1). Furthermore, the same TgMSH-1-dependent cell cycle disruption is observed with the antiparasitic ionophore salinomycin and the DNA alkylating agent methyl nitrosourea. Our results suggest a novel mechanism for the mode of action of monensin and salinomycin on coccidial parasites, in which the drug activates an MSH-1-dependent cell cycle checkpoint by an unknown mechanism, ultimately leading to the death of the parasite. This model would indicate that cell cycle disruption is an important mediator of drug susceptibility and resistance to ionophoric antibiotics in coccidian parasites.

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Section: Vol 55 2011mentioning

confidence: 99%

The Antibiotic Monensin Causes Cell Cycle Disruption ofToxoplasma gondiiMediated through the DNA Repair Enzyme TgMSH-1

Lavine

Arrizabalaga

2011

Antimicrob Agents Chemother

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“…In nucleated cells, Na + entry and subsequent cell swelling may be elicited by monensin (rumensin), a well known Na + ionophore, which thus stimulates necrosis rather than apoptosis [22,23]. The effect of monensin may be due to mitochondrial damage [23] and/or weakening of the antioxidative defence [24]. Monensin intoxication leads to severe rhabdomyolysis and acute renal failure with ultimate death of the patients [22,25].…”

Section: Introductionmentioning

confidence: 99%

Monensin Induced Suicidal Erythrocyte Death

Bhavsar

Eberhard

Bobbala

et al. 2010

Cell Physiol Biochem

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Eryptosis, the suicidal erythrocyte death, is characterized by cell membrane scrambling and cell shrinkage. Eryptosis may be triggered by excessive hyperosmotic or isosmotic cell shrinkage leading to increase of cytosolic Ca²⁺ concentration. Eryptosis is further stimulated by the K⁺ ionophore valinomycin, which leads to exit of KCl and osmotically obliged water, or by energy (glucose) depletion, which compromises the function of the Na⁺/K⁺ ATPase thus increasing cytosolic Na⁺ concentration. The present study explored whether the Na⁺ ionophore monensin affects erythrocyte cell volume and eryptosis. The cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in FACS analysis, cytosolic Ca²⁺ concentration from Fluo3 fluorescence and the cytosolic ATP concentration from a luciferase-based assay. Within 24 hours, exposure to monensin (0.1-10 µg/ml) significantly increased forward scatter, cytosolic Ca²⁺ concentration and annexin V-binding. Glucose depletion was followed by decreased forward scatter and increased cytosolic Ca²⁺ concentration and annexin V-binding. The effect on forward scatter was partially reversed, the effect on cytosolic Ca²⁺ concentration and annexin V binding augmented by additional treatment with monensin. In conclusion, monensin dissociates the alterations of cell membrane and cell volume in suicidal erythrocyte death.

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“…The increase in LDH activity may be due to an oxidative stress induced in the testis (Gu et al, 1989). This enzyme is an essential component of the metabolic machinery of spermatozoa involved in energy production (Singh et al, 2006). Since degenerating germ cells release the LDH in the seminiferous tubules (Orlando et al, 1994;Singh et al, 2006), the concentration of this enzyme is an indicator of cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…This enzyme is an essential component of the metabolic machinery of spermatozoa involved in energy production (Singh et al, 2006). Since degenerating germ cells release the LDH in the seminiferous tubules (Orlando et al, 1994;Singh et al, 2006), the concentration of this enzyme is an indicator of cytotoxicity. It is plausible that the cytotoxic parameters such as the sperm count and motility are associated with the increased level of LDH due to the release of the latter into extra-cellular spaces.…”

Section: Discussionmentioning

confidence: 99%

A purine nucleoside analogue-acyclovir [9-(2-hydroxyethoxymethyl)-9h-guanine] reversibly impairs testicular functions in mouse

Narayana

2008

J. Toxicol. Sci.

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-The present study was designed to investigate testicular effects of Acyclovir [9-(2-hydroxyethoxymethyl)-9H−guanine] in mouse. Swiss albino male mice (N=6/group/dose/sample time) were treated (i. p.) every day with 4, 16, 32, and 48 mg/kg body weight of Acyclovir for 15 d. The testis was examined for histopathological changes and the seminiferous tubular diameter (STD) and epithelial height (SE) were measured. The sperm count, sperm motility and sperm morphology assay in caudae epididymes, and intra-testicular levels lactate dehydrogenase (LDH) and testosterone were estimated on 7 d, In conclusion, Acyclovir is cytotoxic to germ cells inducing the cellular destruction, and reducing the sperm count and motility, and increasing sperm abnormalities. Further, Acyclovir also caused cellular destruction thus releasing LDH from the cells, and affecting the Leydig cell function. All adverse effects of Acycovir are reversible by 70 d, except the sperm count and LDH level, which appear to be affected over an extended period of time at a higher dose-level.

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Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase and DNA integrity in rat testicular cells in vitro

Cited by 13 publications

References 28 publications

The Antibiotic Monensin Causes Cell Cycle Disruption ofToxoplasma gondiiMediated through the DNA Repair Enzyme TgMSH-1

The Antibiotic Monensin Causes Cell Cycle Disruption ofToxoplasma gondiiMediated through the DNA Repair Enzyme TgMSH-1

Monensin Induced Suicidal Erythrocyte Death

A purine nucleoside analogue-acyclovir [9-(2-hydroxyethoxymethyl)-9h-guanine] reversibly impairs testicular functions in mouse

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