Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus

Lee, Joo H.; Yang, Sihyung; Oh, Jung Mi; Lee, Myung G.

doi:10.1211/jpp.62.01.0001

Cited by 84 publications

(63 citation statements)

References 157 publications

(384 reference statements)

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“…The results on FBG level support the views that streptozotocin increases blood glucose in rats (Altay et al, 2003;Gunelli et al, 2008;Lee et al, 2010;Fernandes et al, 2011) to cause type I diabetes mellitus and that chronic fructose consumption through insulin resistance mechanism causes type II diabetes mellitus (Arikawe et al, 2006). The results also show that ginger exhibits some hypoglyceamic effects (Akhani et al, 2004;Kadnur and Goyal, 2005;Al-Amin et al, 2006;Iranloye et al, 2011).…”

Section: Discussionsupporting

confidence: 76%

Insulin, pioglitazone and Zingiber officinale administrations improve proliferating cell nuclear antigen immunostaining effects on diabetic and insulin resistant rat testis

Daramola¹,

Olatunji-Bello²,

Obika³

2013

jecm

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Article HistoryReceived 28 / 09 / 2012 Accepted 03 / 11 / 2012 This study accessed the effects of hypoglycaemic drugs on spermatogenesis in diabetic and insulin resistant rat testis following proliferating cell nuclear antigen (PCNA) immunostaining. Male adult Sprague-Dawley rats (120-140 g) were randomly divided into 5 groups. Group 1 served as control group; fed on normal rat pellets. Group 2 served as streptozotocin-insulin treated group; received a single dose IP Injection of streptozotocin 45 mg/kg BW in Na + citrate buffer pH 4.5 and treated with insulin sub-cutaneously. Group 3 served as streptozotocin-ginger treated group; received a single dose IP injection of streptozotocin as in group 2 above and treated with 500 mg/Kg ginger extract orally. Group 4 served as Insulin resistant-pioglitazone treated group; fed ad libitum on a special diet containing 25% fructose mixed with 75% normal rat chow (w/w) and treated with Pioglitazone 15 mg/kg orally. Group 5 served as Insulin resistant-ginger treated group; fed ad libitum on a special diet as in group 4 above, and also treated with 500 mg/Kg ginger extract orally. Following hyperglycemia confirmation, animals were perfused with 4% Paraformaldehyde (PFA). Testes were isolated, and fixed in 4% PFA overnight, embedded in paraffin, 5µm thick sections were made and mounted on poly-L-lysine coated slides. Immunohistochemical staining was carried out on positively charged slides using PCNA as primary antibody. The results showed that insulin, pioglitazone and ginger administrations ameliorated the diabetic and insulin resistant effects on spermatogenesis in male rats. The precise interplay of hypothalamic, pituitary and steroid hormones is subject for further study in these group of animals.

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Section: Discussionsupporting

confidence: 76%

Insulin, pioglitazone and Zingiber officinale administrations improve proliferating cell nuclear antigen immunostaining effects on diabetic and insulin resistant rat testis

Daramola¹,

Olatunji-Bello²,

Obika³

2013

jecm

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“…A diabetic animal model induced by STZ has been widely used in pharmacokinetic studies (Sato et al, 1991;Shimojo et al, 1993;Ogata et al, 1996;Lee et al, 2010;Liu et al, 2010;Yu et al, 2010a), but the real mechanism altering the pharmacokinetics of drugs is unclear. Several studies demonstrated that changes in pharmacokinetics in diabetic rats induced by STZ is mainly due to the indirect effect of STZ (Ioannides et al, 1996;Lee et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies demonstrated that changes in pharmacokinetics in diabetic rats induced by STZ is mainly due to the indirect effect of STZ (Ioannides et al, 1996;Lee et al, 2010). The complications from any toxic effects of STZ were negligible 4 to 5 weeks after STZ injection (Watkins and Sherman, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Opposite Effect of Diabetes Mellitus Induced by Streptozotocin on Oral and Intravenous Pharmacokinetics of Verapamil in Rats

Hu¹,

Xie²,

Liu³

et al. 2010

Drug Metab Dispos

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ABSTRACT:The aim of this study was to report the effect of diabetes mellitus on the pharmacokinetics of verapamil in a route-dependent manner. Diabetes in rats was induced by streptozotocin. Plasma concentrations of verapamil and its metabolite, norverapamil, were measured after oral (10 mg/kg) or intravenous (1 mg/kg) administration. The concentrations of verapamil in portal plasma after oral administration were also determined. Norverapamil formation was used for assessing CYP3A activity in hepatic and intestinal microsomes of diabetic rats. The protein levels of CYP3A1 and CYP3A2 in liver and intestine were measured by Western blot. It was found that diabetes significantly increased the plasma concentration of verapamil and norverapamil after oral administration, which resulted in a 74% increase in the area under the concentration-time curve (AUC) of verapamil, but the ratio of AUC (norverapamil) /AUC (verapamil) was significantly decreased by 38%. In contrast, diabetes significantly decreased the AUC of verapamil by 22% after intravenous administration. Diabetes also resulted in increased AUC of verapamil in portal vein by 3.8-fold compared with that in control rats. The absolute bioavailability of verapamil was higher than that of control rats. An in vitro study showed that increased CYP3A activity in the hepatic microsome and decreased CYP3A activity in the intestinal microsome were accompanied by an increase and decrease in the protein expression of CYP3A1/2 in liver and intestine of diabetic rats, respectively. In conclusion, diabetes mellitus revealed a tissue-specific effect on CYP3A activity and expression (induced in liver and inhibited in intestine), resulting in opposite pharmacokinetic behaviors of verapamil after oral and intravenous administration to diabetic rats.

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“…Since the solutions of alloxan and streptozotocin are relatively unstable, they should be prepared immediately before the injection. Note that these substances can possess different degrees of toxicity with respect to other organs, too [9,90,91]. Besides the destruction of beta cells, alloxan and streptozotocin are capable of modifying biological macromolecules and DNA fragmenting [9,10,11,89].…”

Section: Experimental Models Of Diabetes Mellitusmentioning

confidence: 99%

Optical and structural properties of biological tissues under diabetes mellitus

Tuchina

Tuchin

2018

J-BPE

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Abstract. Diabetes mellitus is a serious social and economic problem of modern society because it is widespread and fraught with numerous complications. Therefore, it is necessary to search for new methods of diabetes mellitus diagnostics and treatment and to improve the existing ones, which, in turn, requires thorough investigation of the disease development mechanisms, as well as elaboration of simple and reliable methods and criteria for detecting the complication precursors. In connection with the solution of these problems, in the paper we present an analytical review of recent publications devoted to the study of the changes of structural and optical properties of biological tissues under the conditions of diabetes mellitus development using in vitro models of glycated tissues, in vivo experimental models of diabetes in laboratory animals, and clinical studies.

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Pharmacokinetics of drugs in rats with diabetes mellitus induced by alloxan or streptozocin: comparison with those in patients with type I diabetes mellitus

Cited by 84 publications

References 157 publications

Insulin, pioglitazone and Zingiber officinale administrations improve proliferating cell nuclear antigen immunostaining effects on diabetic and insulin resistant rat testis

Insulin, pioglitazone and Zingiber officinale administrations improve proliferating cell nuclear antigen immunostaining effects on diabetic and insulin resistant rat testis

Opposite Effect of Diabetes Mellitus Induced by Streptozotocin on Oral and Intravenous Pharmacokinetics of Verapamil in Rats

Optical and structural properties of biological tissues under diabetes mellitus

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