Protective effects of lipoic acid and mesna on cyclophosphamide‐induced haemorrhagic cystitis in mice

Abstract

The protective roles of lipoic acid (LA)/vitamin C (VC) and mesna on preventing cyclophosphamide (CYP)-induced haemorrhagic cystitis (HC) were investigated. Swiss mice were divided into five groups randomly. HC was induced by a single dose of CYP injection (150-mg kg(-1) bodyweight). Group I was injected with saline (four times in total) throughout as control group. Group II received CYP and three equal doses of saline. Group III received CYP and three doses of mesna, whereas Group IV (or Group V) received CYP, mesna + two doses of VC (or LA). All injections were performed intraperitoneally. After 24 h of cystitis induction, the bladders were collected for all the experiments. Histological characterization showed that CYP injection resulted in severe HC. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances' levels were increased in CYP group. The activities of antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase, were inhibited significantly in CYP groups, respectively. In addition, activation of c-jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in the mechanism of CYP-induced HC but not extracellular signal regulated kinases (ERK). Significant suppression of p38 phosphorylation on Group V suggests that LA and mesna may have synergistic beneficial effect. In Groups III-V, all the parameters of HC and oxidative stress were inhibited significantly. Taking together, we found that these results illustrated that ROS play an important role on CYP-induced HC and the administration of LA/VC with mesna may have therapeutic potential against CYP-induced bladder HC.

Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice

“…administration of cyclophosphamide (Fig. 3), in agreement with independent evidence in mice (26). Systemic preadministration of polaprezinc at 400 mg/kg significantly prevented the cyclophosphamide-induced increase in the bladder malondialdehyde levels (Fig.…”

Prevention of cyclophosphamide-induced hemorrhagic cystitis by resveratrol: a comparative experimental study with mesna

“…Decreased activity of the enzymatic antioxidants such as SOD, CAT and GPx has been well demonstrated in CP toxicity [25,37,43]. Treatment with mesna and antioxidants (lipoic acid) restored the enzyme activities to some extent [32]. In the present study, SOD, CAT, and GPx activities significantly decreased in CP-administered rats when compared to the sham group.…”

“…a p < 0.05 with respect to control, b p < 0.01 with respect to control, c p < 0.001 with respect to control causes a significant increase in ROS level in bladder tissues. Administration of antioxidants ameliorates oxidative stress by reducing ROS levels in bladder tissues [32]. Several antioxidants, such as α-tocopherol [24], β-carotene [33], and melatonin [34,35] have similar effects on cystitis symptoms [11].…”

“…The accumulation of acrolein in the bladder can cause HC. This major side effect limits the use of CP in the clinical field [32]. Current knowledge provides information about the pathophysiological mechanism of HC.…”

The effect of vitamin C supplementation on neutropenia induced by cyclophosphamide in mice

“…This micronutrient has low cost, is easily accessible and safe 10 . In addition, supplementation of vitamin C in combination with cytotoxic agents in experimental models with CLF has shown therapeutic potential 11,12,13 . Previous studies concluded that vitamin C supplementation is nephroprotective in mice exposed to cisplatin 14,15 , indicating that this nutrient can be beneficial when administered in combination with chemotherapy agents.…”