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Effects of pretreatment with single-dose or intermittent oxygen on Cisplatin-induced nephrotoxicity in rats.

Rasoulian B, Kaeidi A, Pourkhodadad S, Dezfoulian O, Rezaei M, Wahhabaghai H, Alirezaei M - Nephrourol Mon (2014)

Bottom Line: The beneficial effects of pretreatment with O2 on renal structure and function were seen if CP was administrates seven days after pretreatment with intermittent O2.The pattern of pretreatment with O2 could change this potential and highly protective strategy against CP-induced nephropathy to an ineffective or even mildly deteriorating one.Therefore, O2 administration before CP injection to patients with cancer, for therapeutic purposes or as a preconditioning approach, should be performed and investigated with caution until exact effects of different protocols has been determined in human.

View Article: PubMed Central - PubMed

Affiliation: Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, IR Iran ; Department of Physiology and Pharmacology, Lorestan University of Medical Sciences, Khorramabad, IR Iran.

ABSTRACT

Background: Renal injury is the main side effect of cisplatin (CP), an anticancer drug. It has been shown that pretreatment with single-dose oxygen (0.5 to six hours) could reduce CP-induced renal toxicity in rats.

Objectives: The present study aimed to compare the effects of pretreatment with single-dose and intermittent O2 on CP-induced nephrotoxicity.

Materials and methods: Adult male rats were allocated to seven groups (eight rats in each group). The rats were kept in normal air or hyperoxic environment (O2, 80%) for either a single six-hour period or intermittent six hours per day for seven days and then were subjected to intraperitoneal injection of saline or CP (5 mg/kg) at 48 hours, 72 hours, or seven days after exposure to O2. Three days after CP (or Saline) injection, renal function tests, renal tissue injury scores, and cleaved Caspase-3 and Bax/Bcl-2 genes expression (as markers of renal cell apoptosis) were assessed.

Results: Treatment with the 6-hour single-dose O2 reduced renal injury significantly when CP was administrated 48 hours after O2 pretreatment. Pretreatment with intermittent seven days of six hours per day had no protective effects and even relatively worsened renal injury when CP was injected 48 hours or 72 hours after the last session of O2 pretreatment. The beneficial effects of pretreatment with O2 on renal structure and function were seen if CP was administrates seven days after pretreatment with intermittent O2.

Conclusions: The pattern of pretreatment with O2 could change this potential and highly protective strategy against CP-induced nephropathy to an ineffective or even mildly deteriorating one. Therefore, O2 administration before CP injection to patients with cancer, for therapeutic purposes or as a preconditioning approach, should be performed and investigated with caution until exact effects of different protocols has been determined in human.

No MeSH data available.


Related in: MedlinePlus

Renal Function TestsFor explanation about different groups, see text (***, P ≤ 0.005 in comparison with “Air + CP” group; **, 0.005 < P ≤ 0.01 in comparison with “Air + CP” group; *, 0.01 < P ≤ 0.05 in comparison with “Air + CP” group; a, 0.05 < P ≤ 0.08 in comparison with “Air + CP” group; and #, insignificantly different from “Air + Saline” group).
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fig13019: Renal Function TestsFor explanation about different groups, see text (***, P ≤ 0.005 in comparison with “Air + CP” group; **, 0.005 < P ≤ 0.01 in comparison with “Air + CP” group; *, 0.01 < P ≤ 0.05 in comparison with “Air + CP” group; a, 0.05 < P ≤ 0.08 in comparison with “Air + CP” group; and #, insignificantly different from “Air + Saline” group).

Mentions: Administration of single-dose O2 to group 3 (6hO2 48hLCP) for six hours led to considerable and significant reduction in both blood urea and Cr levels in this group in comparison with “Air + CP” (P < 0.005) but it showed no significant differences with “Air + Saline” and “O2+Saline” groups. The difference in CLCr was insignificant between “6hO2 48hLCP” and “Air + CP” groups (P = 0.089); moreover, there was no significant differences between group 3 and any of groups 1 and 2 (P = 0.18 and P = 0.47, respectively). Seven days of six hours per day administration of O2 had no significant effect on any of renal function tests if CP was injected 48 hours or 72 hours after last session of O2 administration (no differences between groups 4 or 5 and group 7). Some degree of renal function amelioration was seen if CP was administrated seven days after this protocol of O2 administration (significant or marginally significant reduction in plasma urea and Cr levels, respectively, in comparison with group 7,). CLCr in “7dayO2 7dayLCP” group was not significantly different from “Air + CP” group but it was significantly and marginally significantly less than group 1 (P = 0.015) and group 2, respectively (P = 0.063). There was an insignificant deterioration of all these three renal function indicators in groups 4 and 5 in comparison to the control group (Figure 1).


Effects of pretreatment with single-dose or intermittent oxygen on Cisplatin-induced nephrotoxicity in rats.

Rasoulian B, Kaeidi A, Pourkhodadad S, Dezfoulian O, Rezaei M, Wahhabaghai H, Alirezaei M - Nephrourol Mon (2014)

Renal Function TestsFor explanation about different groups, see text (***, P ≤ 0.005 in comparison with “Air + CP” group; **, 0.005 < P ≤ 0.01 in comparison with “Air + CP” group; *, 0.01 < P ≤ 0.05 in comparison with “Air + CP” group; a, 0.05 < P ≤ 0.08 in comparison with “Air + CP” group; and #, insignificantly different from “Air + Saline” group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318017&req=5

fig13019: Renal Function TestsFor explanation about different groups, see text (***, P ≤ 0.005 in comparison with “Air + CP” group; **, 0.005 < P ≤ 0.01 in comparison with “Air + CP” group; *, 0.01 < P ≤ 0.05 in comparison with “Air + CP” group; a, 0.05 < P ≤ 0.08 in comparison with “Air + CP” group; and #, insignificantly different from “Air + Saline” group).
Mentions: Administration of single-dose O2 to group 3 (6hO2 48hLCP) for six hours led to considerable and significant reduction in both blood urea and Cr levels in this group in comparison with “Air + CP” (P < 0.005) but it showed no significant differences with “Air + Saline” and “O2+Saline” groups. The difference in CLCr was insignificant between “6hO2 48hLCP” and “Air + CP” groups (P = 0.089); moreover, there was no significant differences between group 3 and any of groups 1 and 2 (P = 0.18 and P = 0.47, respectively). Seven days of six hours per day administration of O2 had no significant effect on any of renal function tests if CP was injected 48 hours or 72 hours after last session of O2 administration (no differences between groups 4 or 5 and group 7). Some degree of renal function amelioration was seen if CP was administrated seven days after this protocol of O2 administration (significant or marginally significant reduction in plasma urea and Cr levels, respectively, in comparison with group 7,). CLCr in “7dayO2 7dayLCP” group was not significantly different from “Air + CP” group but it was significantly and marginally significantly less than group 1 (P = 0.015) and group 2, respectively (P = 0.063). There was an insignificant deterioration of all these three renal function indicators in groups 4 and 5 in comparison to the control group (Figure 1).

Bottom Line: The beneficial effects of pretreatment with O2 on renal structure and function were seen if CP was administrates seven days after pretreatment with intermittent O2.The pattern of pretreatment with O2 could change this potential and highly protective strategy against CP-induced nephropathy to an ineffective or even mildly deteriorating one.Therefore, O2 administration before CP injection to patients with cancer, for therapeutic purposes or as a preconditioning approach, should be performed and investigated with caution until exact effects of different protocols has been determined in human.

View Article: PubMed Central - PubMed

Affiliation: Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, IR Iran ; Department of Physiology and Pharmacology, Lorestan University of Medical Sciences, Khorramabad, IR Iran.

ABSTRACT

Background: Renal injury is the main side effect of cisplatin (CP), an anticancer drug. It has been shown that pretreatment with single-dose oxygen (0.5 to six hours) could reduce CP-induced renal toxicity in rats.

Objectives: The present study aimed to compare the effects of pretreatment with single-dose and intermittent O2 on CP-induced nephrotoxicity.

Materials and methods: Adult male rats were allocated to seven groups (eight rats in each group). The rats were kept in normal air or hyperoxic environment (O2, 80%) for either a single six-hour period or intermittent six hours per day for seven days and then were subjected to intraperitoneal injection of saline or CP (5 mg/kg) at 48 hours, 72 hours, or seven days after exposure to O2. Three days after CP (or Saline) injection, renal function tests, renal tissue injury scores, and cleaved Caspase-3 and Bax/Bcl-2 genes expression (as markers of renal cell apoptosis) were assessed.

Results: Treatment with the 6-hour single-dose O2 reduced renal injury significantly when CP was administrated 48 hours after O2 pretreatment. Pretreatment with intermittent seven days of six hours per day had no protective effects and even relatively worsened renal injury when CP was injected 48 hours or 72 hours after the last session of O2 pretreatment. The beneficial effects of pretreatment with O2 on renal structure and function were seen if CP was administrates seven days after pretreatment with intermittent O2.

Conclusions: The pattern of pretreatment with O2 could change this potential and highly protective strategy against CP-induced nephropathy to an ineffective or even mildly deteriorating one. Therefore, O2 administration before CP injection to patients with cancer, for therapeutic purposes or as a preconditioning approach, should be performed and investigated with caution until exact effects of different protocols has been determined in human.

No MeSH data available.


Related in: MedlinePlus