Pharmacological Blockage of Serotonin Biosynthesis and Circadian Changes in Oxaliplatin Toxicity in Rats

Boughattas, Naceur A.; Attia, Mossadok Ben; Ixart, G.; Lemaigre, G; Mechkouri, Mohamed; Reinberg, A

doi:10.1081/cbi-120015957

Cited by 6 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In rodents and other mammals, most circadian rhythms are controlled and=or regulated by the SCN, which depends in part on the serotoninergic system (Rietveld, 1992). Boughattas et al (2002). Best drug tolerance occurred when the drug was injected in the light phase (during the animals' rest span).…”

Section: Discussionmentioning

confidence: 99%

“…The effects of the neurotoxic agent pCPA, which inhibits serotonin biosynthesis, are dosing-time dependent as shown by Ixart et al (1985) and (1,7,13,and 19 HALO) in 100 Swiss albino male mice. The agent pCPA obliterates the circadian rhythm in plasma ACTH in a dosing-time dependent manner, but not that in corticosterone or leucocytes (Boughattas et al, 2002;Ixart et al, 1985). Boughattas et al (2002).…”

Section: Discussionmentioning

confidence: 99%

“…Best drug tolerance occurred when the drug was injected in the light phase (during the animals' rest span). In rats whose serotonin biosynthesis was blocked, the circadian rhythms in the toxic effects of l-OHP and ACTH were obliterated, whereas the rhythms in corticosterone and leukocytes persisted (Boughattas et al, 2002). The agent pCPA obliterates the circadian rhythm in plasma ACTH in a dosing-time dependent manner, but not that in corticosterone or leucocytes (Boughattas et al, 2002;Ixart et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

“…As shown by Boughattas et al (2002), the chronotoxic effects of the anticancer medication l-OHP are influenced by pCPA and presumably the SCN. Usually the 8h period is interpreted to be a component harmonic of the 24h fundamental period that contributes to the overall description of the waveform shape of the 24h temporal pattern.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Circadian Rhythms in Toxic Effects of the Serotonin Antagonist Ondansetron in Mice

Khedhaier

Attia²,

Gadacha³

et al. 2003

Chronobiology International

Self Cite

View full text Add to dashboard Cite

The aim of the study was to learn whether the lethal and the motor incoordination (ataxia) side effect of ondansetron (Zophren) administration is dosing-time dependent. Ondansetron is a serotonin 5-HT3 receptor antagonist used primarily to control nausea and vomiting arising from cytotoxic chemo- and radiotherapy. A total of 210 male Swiss mice 10 to 12 weeks of age were synchronized for 3 weeks by 12 h light (rest span)/12 h dark (activity span). Different doses of ondansetron were injected intraperitoneally (i.p.) at fixed times during the day to determine both the sublethal (TD50) and lethal (LD50) doses, which were, respectively, 3.7 +/- 0.6 mg/kg and 4.6 +/- 0.5 mg/kg. In the chronotoxicologic study a single dose of ondansetron (3.5 mg/kg, i.p.) was administered to different and comparable groups of animals at four different circadian stages [1, 7, 13, and 19 h after light onset (HALO)]. The lethal toxicity was statistically significantly dosing time-dependent (chi2 = 21.51, p < 0.0001). Drug dosing at 1 HALO resulted in 100% survival rate whereas drug dosing at 19 HALO was only one-half that (52%). Similarly, lowest and highest ataxia occurred when ondansetron was injected at 1 and 19 HALO, respectively (chi2 = 22.24, p < 0.0001). Effects on rectal temperature were also dosing-time related (Cosinor analysis, p < 0.0001). The characteristics of the waveform describing the temporal patterns differed between the studied variables, e.g., lethal toxicity and survival rate showing two peaks and rectal temperature showing one peak in the 24 h time series waveform pattern. Cosinor analysis also revealed a statistically significant ultradian (tau = 8 h) rhythmic component in the considered variables. Differences in curve patterns in toxicity elicited by ondansetron on a per end point basis are hypothesized to represent the phase relations between the identified 24 h and 8 h periodicities.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Circadian Rhythms in Toxic Effects of the Serotonin Antagonist Ondansetron in Mice

Khedhaier

Attia²,

Gadacha³

et al. 2003

Chronobiology International

Self Cite

View full text Add to dashboard Cite

show abstract

“…Treatment of BMCs by L-OHP together with ceefourin resulted in a 5-times increase in Pt accumulation. Ceefourin was originally reported as a human MRP4 inhibitor 29 , but it also induced significant Pt accumulation in mouse MRP4-expressing cells after L-OHP treatment. Ceefourin may exert its inhibitory action on both human and mouse MRP4.…”

Section: Discussionmentioning

confidence: 97%

Diurnal expression of MRP4 in bone marrow cells underlies the dosing-time dependent changes in the oxaliplatin-induced myelotoxicity

Kato

Tsurudome

Kanemitsu

et al. 2020

Sci Rep

View full text Add to dashboard Cite

the expression and function of some xenobiotic transporters varies according to the time of day, causing the dosing time-dependent changes in drug disposition and toxicity. Multidrug resistanceassociated protein-4 (MRP4), an ATP binding cassette (ABC) efflux transporter encoded by the Abcc4 gene, is highly expressed in bone marrow cells (BMCs) and protects them against xenobiotics, including chemotherapeutic drugs. In this study, we demonstrated that MRP4 was responsible for the extrusion of oxaliplatin (L-OHP), a platinum (Pt)-based chemotherapeutic drug, from BMCs of mice, and that the efflux transporter expression exhibited significant diurnal variation. Therefore, we investigated the relevance of the diurnal expression of MRP4 in BMCs for L-OHPinduced myelotoxicity in mice maintained under standardized light/dark cycle conditions. After intravenous injection of L-OHP, the Pt content in BMCs varied according to the injection time. Lower Pt accumulation in BMCs was detected in mice after injection of L-OHP at the mid-dark phase, during which the expression levels of MRP4 increased. Consistent with these observations, the myelotoxic effects of L-OHP were attenuated when mice were injected with L-OHP during the dark phase. This dosing schedule also alleviated the L-OHP-induced reduction of the peripheral white blood cell count. The present results suggest that the myelotoxicity of L-OHP is attenuated by optimizing the dosing schedule. Diurnal expression of MRP4 in BMCs is associated with the dosing time-dependent changes in L-OHP-induced myelotoxicity. Daily variations in biological functions, such as gene expression and protein synthesis, are thought to be important factors affecting the efficacy and/or toxicity of drugs; a large number of drugs cannot be expected to have the same potency at different administration times 1,2. Consequently, administration of drugs at appropriate times of day can improve the outcome of pharmacotherapy by maximizing their potency and minimizing their toxicity, whereas drug administration at an inappropriate time of day can induce severe side effects. Dosing time-dependent differences in the drug effects are due, at least in part, to 24-h changes in drug disposition such as absorption, distribution, metabolism, and elimination 3-6. ATP binding cassette (ABC) transporters are widely known as energy-dependent efflux pumps that expel cytotoxic substances, including chemotherapeutic drugs. They are expressed in epithelial cells of several organs, including the brain, liver, intestine, and kidney 7 , and function as a barrier to limit intestinal absorption of many drugs and their distribution to different tissues 8. Furthermore, several types of ABC transporters also function in the biliary, intestinal, and renal elimination of drugs 9. The expression and function of some ABC transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer-resistant protein (BCRP), exhibit diurnal variation, resulting in dosing time-dependent differences i...

show abstract

Involvement of serotonin in the hypoglycemic response to 2Hz electroacupuncture of zusanli acupoint (ST36) in rats

Chang

Tsai

Lin

et al. 2005

Neuroscience Letters

View full text Add to dashboard Cite

Pharmacological Blockage of Serotonin Biosynthesis and Circadian Changes in Oxaliplatin Toxicity in Rats

Cited by 6 publications

References 19 publications

Circadian Rhythms in Toxic Effects of the Serotonin Antagonist Ondansetron in Mice

Circadian Rhythms in Toxic Effects of the Serotonin Antagonist Ondansetron in Mice

Diurnal expression of MRP4 in bone marrow cells underlies the dosing-time dependent changes in the oxaliplatin-induced myelotoxicity

Involvement of serotonin in the hypoglycemic response to 2Hz electroacupuncture of zusanli acupoint (ST36) in rats

Contact Info

Product

Resources

About