Effect of Caffeic Acid on Ischemia-Reperfusion-Induced Acute Renal Failure in Rats.

BACKGROUND: Cyclooxygenase (COX)-lipooxygenase (LOX) pathway plays a key role in the pathogenesis of renal ischemia/reperfusion (IR). OBJECTIVE: This study was aimed to evaluate the role of dietary phenol caffeic acid (CA), alone and in combination with selective COX-2 inhibitor celecoxib (CEL) in IR-induced acute renal failure (ARF) in rats. MATERIALS AND METHODS: Renal IR was induced by bilateral occlusion of renal pedicels for 90 min followed by reperfusion for 24 h. Rats were randomized into 4 groups: Sham, IR, CA + IR, and CA + CEL + IR, with 7 day treatment before IR. Serum creatinine (SCr), blood urea nitrogen (BUN), antioxidant enzymes, tumor necrosis factor alpha (TNF-α), and histopathological changes were evaluated in the kidney after IR. RESULTS: Renal IR caused significant derangement in renal function and histology. In the IR group, an increase in lipid peroxidation and decreased antioxidant defense enzyme activity were observed. Pretreatment with CA and CA + CEL showed a significant decrease in the BUN, SCr, TNF-α, oxidative stress markers and corrected the histological changes in the kidney. CONCLUSION: This study demonstrated the renoprotective potential of CA and combination of CA + CEL in IR-induced ARF in rats. The plausible mechanisms for the efficacy of CA could be attributed to its ability to modulate the -COX-LOX system in renal IR.

Effect of insulin on spatial memory in aluminum chloride-induced dementia in rats.

Latest reports suggest the involvement of insulin in modulating memory. A few published in-vitro studies favor the antidementia effect of insulin. Thus, the present study aimed to evaluate the prophylactic role of insulin and its combination with glucose and its possible mechanism(s) in an aluminum chloride (AlCl3)-induced cognitive dysfunction model in rodents, with a special focus on memory centers namely, the hippocampus and the frontal cortex. Male Wistar rats were exposed to AlCl3 (175 mg/kg orally) for 60 days. Insulin (0.5 IU/kg), Insulin (0.5 IU/kg) in combination with glucose (200 mg/kg), and rivastigmine (1 mg/kg) were administered intraperitoneally 45 min before the administration of AlCl3 for 60 days. Spatial memory was assessed using the Morris water-maze test. After 60 days of treatment, animals were killed, and the hippocampus and frontal cortex were collected and analyzed for acetylcholinesterase activity and antioxidant enzyme level. Blood glucose levels were also analyzed. Treatment with the standard drug, rivastigmine (1 mg/kg), produced a significant reduction in escape latency and increased the time spent in the target quadrant compared with the AlCl3-treated group. Insulin and its combination with glucose could not inhibit the behavioral impairments in aluminum-exposed rats. Treatment with insulin alone and its combination with glucose reversed the increased glucose levels. Insulin alone and its combination with glucose could not inhibit aluminum-induced oxidative stress and impaired cholinergic transmission in the hippocampus and frontal cortex regions. The study suggests the inability of prophylactic insulin administration against cognitive dysfunction induced by environmental toxin (AlCl3) in the hippocampus and the frontal cortex.

Naringin and Rutin Alleviates Episodic Memory Deficits in Two Differentially Challenged Object Recognition Tasks.

BACKGROUND: Cognitive decline or dementia is a debilitating problem of neurological disorders such as Alzheimer's and Parkinson's disease, including special conditions like chemobrain. Dietary flavonoids proved to be efficacious in delaying the incidence of neurodegenerative diseases. Two such flavonoids, naringin (NAR) and rutin (RUT) were reported to have neuroprotective potential with beneficial effects on spatial and emotional memories in particular. However, the efficacy of these flavonoids is poorly understood on episodic memory, which comprises an important form of autobiographical memory. OBJECTIVE: This study objective is to evaluate NAR and RUT to reverse time-delay-induced long-term and scopolamine-induced short-term episodic memory deficits in Wistar rats. MATERIALS AND METHODS: We have evaluated both short-term and long-term episodic memory forms using novel object recognition task. Open field paradigm was used to assess locomotor activity for any confounding influence on memory assessment. Donepezil was used as positive control and was effective in both models at 1 mg/kg, i.p. RESULTS: Animals treated with NAR and RUT at 50 and 100 mg/kg, p.o. spent significantly more time exploring novel object compared to familiar one, whereas control animals spent almost equal time with both objects in choice trial. NAR and RUT dose-dependently increased recognition and discriminative indices in time-induced long-term as well as scopolamine-induced short-term episodic memory deficit models without interfering with the locomotor activity. CONCLUSION: We conclude that, NAR and RUT averted both short- and long-term episodic memory deficits in Wistar rats, which may be potential interventions for neurodegenerative diseases as well as chemobrain condition. SUMMARY: Incidence of Alzheimer's disease is increasing globally and the current therapy is only symptomatic. Curative treatment is a major lacuna. NAR and RUT are natural flavonoids proven for their pleiotropic pharmacological effects with potential neuroprotective benefits. The study evaluated these flavonoids for their potential to improve the most common form of episodic memory (memory of autobiographical events in relation to time, places etc.) in two differential animal models assessing short-term and long-term memory, respectively. We also found that NAR and RUT were able to reverse both short-term and long-term memory deficits dose dependently in female Wistar rats. Abbreviations used: AD: Alzheimer's disease, AChE: Acetylcholinesterase, COX: Cyclooxygenase, DI: Discriminative index, ITI: Inter trial interval, NAR: Naringin, RUT: Rutin, NORT: Novel object recognition task, NOS: Nitric oxide synthase, QOL: Quality of life, RI: Recognition index, WFI: Water for injection.

Preliminary evaluation of in vitro cytotoxicity and in vivo antitumor activity of Xanthium strumarium in transplantable tumors in mice.

In the present study, active fractions of the methanolic extract of Xanthium strumarium (XS) showing potent cytotoxicity were determined using microculture tetrazolium (MTT) and sulforhodamine B (SRB) assays in selected cancer cell lines. The active fractions viz., chloroform soluble fraction of root (CEXSR), hexane soluble fraction of leaf (HEXSL), hexane soluble fraction of fruits (HEXSF) and chloroform soluble fraction of fruits (CEXSF) of XS were tested in transplantable animal tumor models for their antitumor potential. Dalton's ascitic lymphoma (DLA) cells were used to induce solid and liquid (ascites) tumor in mice. The tumor bearing animals were treated with active fractions at two dose levels (100 and 200 mg/kg). The antitumor activities of the active fractions in tumor bearing animals were monitored with parameters such as body weight and increase in life-span as well as biochemical and hematological modalities (in the case of liquid tumor). Tumor incidence and tumor volume were the parameters monitored in the case of the solid tumor model. The results were analyzed by one-way ANOVA followed by Tukey's post hoc test. The extracts were found to increase the life-span of tumor bearing animals and restore the altered hematological and biochemical parameters significantly.