The effect of Thespesia populnea on cisplatin induced nephrotoxicity.

AIM OF THE STUDY: To study the effect of Thespesia populnea on Cisplatin induced Nephrotoxicity. MATERIALS AND METHODS: Experiments were conducted on Male Sprague Dawley Rats (4-6 weeks old) weighing 100-120g B.Wt. The drug under study was cisplatin, which is an anticancer drug. Thespesia populnea extract was used to test its ability to alleviate the harmful effects of cisplatin. The animals were divided into three groups: Group I was considered as normal, Group II was given a single dose of cisplatin (6 mg/kg/b.wt., i.p) and they constituted the control animals and Group III was treated with cisplatin along with Thespesia populnea (5 mg/kg/b.wt., i.p) for 10 consecutive days. RESULTS: Administration of cisplatin resulted in significant (P < 0.05) increase in the levels of serum urea (137 ± 1.6), creatinine (1.69 ± 0.14), ALT (96.18 ± 3.44), AST (80.84 ± 3.34) and bilirubin (4.57 ± 0.08) as compared to normal animals. On the other hand, introduction of Thespesia populnea extract caused a significant (P < 0.05) reduction in the levels of serum markers namely urea (112 ± 2.16), creatinine (0.54 ± 0.004), ALT (76.4 ± 1.45), AST (58.80 ± 1.6) and bilirubin (3.96 ± 0.85). DISCUSSION: Increase in the levels of urea and creatinine in serum as well as ALT, AST and bilirubin is suggestive of both kidney and liver damage. Thespesia populnea extract ameliorated cisplatin induced kidney and liver damage as indicated by reduction in the levels of serum urea, creatinine, AST, ALT and bilirubin. Reduction in the levels of these biochemical markers is an indication of regeneration process. Thus it is concluded that the extract might contain nephroprotective compounds such as flavonoids, alkaloids, etc. which are responsible for alleviating cisplatin induced toxicity.

Experimental study on anti-tumor and anti-inflammatory effect of Thespesia populnea phytochemical extract in mice models.

In the present study, we have conducted a dose- and duration-dependent response of phytochemical extract of Thespesia populnea (Malvaceae) plant native of costal forest of India. Our earlier studies revealed the anti-oxidant and chemoprotective effect of this plant extract. In the present study, we have attempted to study the anti-tumor and anti-inflammatory response of T. populnea using experimental mouse models. Our studies revealed that administration of T. populnea methanol extract was shown to inhibit the solid tumor development in mice. T. populnea treatment significantly reduced tumor cell glutathione (GSH) levels as well as serum γ-glutamyl transpeptidase (GGT) and nitric oxide (NO) levels in the tumor-bearing animals (p < 0.01). The total white blood cell count and hemoglobin levels were also significantly increased in extract-treated hosts (p < 0.05, p < 0.01). The use of T. populnea substantially reduced the acute inflammation (assessed as paw edema) induced by carrageenan and also reduced inflammation edema induced by formalin. These studies suggest that T. populnea extract could be used as a (natural) anti-inflammatory and anti-tumor agent.

Tumour lysis syndrome: implications for cancer therapy.

The tumour lysis syndrome (TLS) is a group of metabolic abnormalities caused by rapid and unexpected release of cellular components into the circulation as a result of massive destruction of rapidly proliferating malignant cells. It usually develops in patients with hematologic malignancies like acute lymphoid leukemia, non-Hodgkin and Burkitt's lymphoma after initiation of chemotherapy or may, rarely, occur spontaneously. Though TLS is seldom observed in relation to solid tumours, there have been reports of connections with examples such as lung, liver, breast, gastric carcinomas. The clinical manifestations of TLS include hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These indications if untreated lead to life-threatening complications such as acute renal failure, cardiac arrhythmias, seizures, and eventually death due to multiorgan failure. Therefore early detection of TLS is of vital importance. This can be accomplished by identification of high risk patients, implementation of suitable prophylactic measures and monitoring of the electrolyte levels in patients undergoing chemotherapy.

Chemoprotective and immunomodulatory effect of Acacia nilotica during cyclophosphamide induced toxicity.

Most of the synthetic chemotherapeutic agents used today are immunosuppressant and lead to numerous side effects. Plant based immunomodulators are employed as supportive therapy to counteract the undesirable side effects of chemotherapy. In the present study, the immunomodulatory and chemoprotective effect of methanolic extract of Acacia nilotica was investigated in mice. Intraperitoneal administration of the extract was found to significantly increase the Total WBC count, bone marrow cellularity and alpha-esterase positive cells. Cyclophosphamide is a chemotherapeutic drug and induces acute myelosuppression but treatment with the extract was beneficial in ameliorating chemically induced toxicity. The administration of the extract considerably increased the Total WBC count (6800 +/- 733.9 cells/cm2), bone marrow cellularity (43.6 x 10(5) +/- 14.33 cells/femur) and alpha-esterase positive cells (808.6 +/- 8.57 cells/4000 cells) in CTX treated mice when compared to CTX alone treated control mice. Weight of lymphoid organs such as spleen and thymus reduced by CTX were enhanced by treatment with Acacia nilotica extract. It can be concluded that the extract possess immunostimulatory properties.

Myeloperoxidase: the yin and yang in tumour progression.

Myeloperoxidase (MPO) is a heme- containing enzyme abundantly expressed in neutrophils. It catalyzes the reaction between chloride and hydrogen peroxide to generate a potent oxidant, hypochlorous acid (HOCl). It plays an important role in innate immune defense mechanism. However, excessive generation of MPO-derived oxidants has been linked to tissue damage and in the initiation and progression of diseases such as cancer which arise from chronic inflammation. The oxidant activity of MPO is believed to promote the metabolism of chemical carcinogens, cause DNA damage and compromise the repair process. It is also considered as important mediators of gastric ulcers caused by Helicobacter pylori (H. pylori) through its ability to catalyze the generation of reactive oxidants. A G-463 a polymorphism located in the promoter of the MPO gene plays an important role in its transcription. Moreover the reactive oxidants produced by neutrophilic enzyme have the potential to interact with tumour cells and contribute to their metastasis. There has been a considerable interest in the screening of plant extracts and compounds isolated from them for their potential use as HOCl scavengers. This review will discuss the role of MPO in tumour progression and provide an overview of its part in tumour metastasis and ulcer.