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ORIGINAL ARTICLE
Year : 2013  |  Volume : 9  |  Issue : 1  |  Page : 50-53

The effect of Thespesia populnea on cisplatin induced nephrotoxicity


Department of Biotechnology, School of Biotechnology and Health Sciences, Karunya University, Karunya Nagar, Coimbatore, Tamil Nadu, India

Date of Web Publication10-Apr-2013

Correspondence Address:
Chandrasekaran Guruvayoorappan
Department of Biotechnology, School of Biotechnology and Health Sciences, Karunya University, Karunya Nagar, Coimbatore - 641 114, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.110362

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 > Abstract 

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.

Keywords: Cisplatin, kidney, nephrotoxicity, Thespesia populnea, toxicity


How to cite this article:
Mika D, Guruvayoorappan C. The effect of Thespesia populnea on cisplatin induced nephrotoxicity. J Can Res Ther 2013;9:50-3

How to cite this URL:
Mika D, Guruvayoorappan C. The effect of Thespesia populnea on cisplatin induced nephrotoxicity. J Can Res Ther [serial online] 2013 [cited 2019 Nov 19];9:50-3. Available from: http://www.cancerjournal.net/text.asp?2013/9/1/50/110362


 > Introduction Top


Cancer is one of the most dreaded disease and is among the leading cause of death worldwide. Chemotherapy and radiotherapy are the common modalities of cancer treatment. Cisplatin (Cis-diamminedichloro platinum-II) is one of the most potent chemotherapeutic agents available to treat a variety of malignancies including ovarian, lung, head and neck cancers as well as testicular and bladder tumors. [1],[2] However, its clinical usefulness is limited by the development of nephrotoxicity. [3-5] Cisplatin is known to induce dose- dependent nephrotoxicity which restricts the use of high doses to maximise the therapeutic efficacy as high doses of cisplatin also produce hepatotoxicity. [6] Nephrotoxicity can be defined as the renal disease or dysfunction that arises as a direct or indirect result of exposure to medicines and industrial or environmental chemicals. Several mechanisms have been suggested for cisplatin-induced renal toxicity such as apoptosis, inflammatory mechanism and generation of reactive oxygen species. [7] Considerable efforts have been directed towards identifying promising antitumor agents that would preferably exhibit less health hazards. [8] Many compounds (synthetic and natural) are being screened for nephroprotective activity against cisplatin-induced nephrotoxicity and in these studies treatment with plant extracts is quite encouraging. [9],[10],[11],[12],[13] At present, the drug search has targeted the natural agents in the hope that they would augment actions or reduce doses of chemotherapeutic drugs thus, improving the overall performance.

Thespesia populnea Soland ex. Correa (Malvaceae) is a large tree found in tropical regions and coastal forests of India. The plant is used in the treatment of skin diseases such as scabies, psoriasis and eczema. The bark, root and fruit were used against dysentery, cholera and haemorrhoids. [14] The fruits of the plant are used in Ayurveda for the control of diabetes. [15] An Ayurvedic preparation containing Thespesia populnea namely "panchvalkala" possess free radical scavenging activity. [16] The barks and flowers has been reported to possess astringent, hepatoprotective, antioxidant and anti-inflammatory activities in rat. [14],[17],[18],[19] The plant is also known to inhibit tumor formation. [20] Four naturally occurring quinines, vizthespone, thespesone, mansonone-D and mansonone-H have been extracted from heart wood of the plant. [21] The phytochemical study reveals the presence of carbohydrate, protein, tannins, phenol, flavonoids, terpenes, saponins and gums in the ethanolic extract of the bark. [22] The present study is designed to evaluate the protective activity of Thespesia populnea against cisplatin induced nephrotoxicity and hepatotoxicity.


 > Materials and Methods Top


Male Sprague Dawley Rats (4-6 weeks old) of 100-120g B.Wt. were purchased from the Pasteur Institute of India, Coonoor, Tamil Nadu, India. The animals were fed with standard diet (Sai Feeds, Bangalore, India) and water ad libitum. All animal experiments were performed according to the guidelines of the Institutional Animal Ethics Committee.

Cisplatin was purchased from DaburPharma Ltd., Solan (H.P), India. Gum acacia was purchased from Hi-Media, Mumbai, India. Urea, Creatinine, Bilirubin, ALT (Alanine transaminase) and AST (Aspartate transaminase) kits were purchased from Span Diagnostics, Surat. All other chemicals used were analytical reagent grade.

Authenticated Thespesia populnea leaves was collected from Coimbatore. A voucher specimen (BSI/SRC/S/23/2011-12/Tech-757) was deposited in the Botanical Survey of India, Coimbatore. The leaves were shade dried and powdered using a blender. The powder (10g) was subjected for methanol extraction (70% Methanol) using Sohxlet apparatus. The extract was evaporated to dryness and the yield of the extract was found to 6%. For in vivo experiments, the extract was suspended in 1% gum acacia and administered intraperitoneally (5mg/Kg B.Wt.) for 10 consecutive days.

The animals were divided into 3 groups of 6 animals each. Group I served as normal untreated control. Group II and III were administered with single dose of cisplatin.Group III alone received Thespesia populnea extract for 10 consecutive days starting from the same of cisplatin administration.

On Day 11, the animals were euthanized by cervical dislocation. Blood was collected and the serum was separated by centrifugation. The Liver and Kidney were excised immediately, washed with ice cold saline. 25% homogenate of the tissues were prepared using Tris buffer (pH 7.2) and used for biochemical estimations. Urea, Creatinine, Bilirubin, ALT (Alanine transaminase) and AST (Aspartate transaminase) were estimated according to the manufacturer's instructions (Span Diagnostics, Surat).

Statistical analysis: The results were expressed as mean±SD. Statistical evaluation were done using one way ANOVA followed by Dunnett Test. Pvalues less than 0.05 were considered to be statistically significant.


 > Results Top


Administration of cisplatin resulted in significant 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 reduction in the levels of serum 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). Whilst there was a marked increase in the levels of urea, creatinine, ALT, AST and bilirubin in liver and kidney of animals receiving both cisplatin and extract as compared to the levels in control animals (cisplatin treated animals). The serum urea, creatinine, ALT, AST and bilirubin levels in liver were 99.6 ± 2.6, 2.5 ± 0.5, 7.36 ± 0.54, 2.06 ± 0.28, 7.18 ± 0.96, respectively, while the corresponding levels of the serum markers in kidney were 89 ± 3.2, 1.6 ± 0.22, 6.3 ± 0.61, 3.25 ± 0.52 and 3.74 ± 0.4. For details refer to [Table 1], [Table 2], [Table 3], [Table 4], [Table 5] and [Table 6].
Table 1: Effect of Thespesia populnea on urea level in cisplatin induced nephrotoxicity

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Table 2: Effect of Thespesia populnea on creatinine level in cisplatin induced nephrotoxicity

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Table 3: Effect of Thespesia populnea on ALT (SGPT) level in cisplatin induced nephrotoxicity

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Table 4: Effect of Thespesia populnea on AST (SGOT) level in cisplatin induced nephrotoxicity

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Table 5: Effect of Thespesia populnea on Total Bilirubin level in cisplatin induced nephrotoxicity

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Table 6: Effect of Thespesia populnea on Direct Bilirubin level in cisplatin induced nephrotoxicity

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The results of this study showed that cisplatin caused a significant reduction in renal function. Biochemical evidence of renal injury was characterised by elevated levels of serum urea and creatinine. Intraperitoneal injection of cisplatin (6mg/kg) also led to an increase in the levels of ALT, AST and bilirubin in the sera of rats of group II which shows that cisplatin also damages the liver. Administration of Thespesia populnea was found to significantly alleviate the levels of these markers.


 > Discussion Top


Cisplatin is a non-specific cytotoxic agent. A major consequence is the reported nephrotoxicity and hepatotoxicity. A significant increase in serum creatinine and urea levels in the rats after the intraperitoneal administration of cisplatin alone (group II) shows that cisplatin induced kidney dysfunction which is in accordance with previous studies. [23] In renal dysfunction, the serum urea accumulates because the rate of serum urea production exceeds the rate of clearance. Elevations of urea and creatinine levels in the serum are taken as the index of nephrotoxicity. The increase in the levels of ALT, AST and bilirubin in the serum of rats treated with cisplatin alone indicates that at the dose (6mg/kg b.w.), cisplatin also damages the liver. Liver damage can be attributed to the damaged structural integrity of the liver because these enzymes are located in the liver cells and leak out into the circulation after cellular 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. Cisplatin induced nephrotoxicity is considered to be a rapid process involving reaction with proteins in the renal tubules. [24],[25] This renal damage occurs within 1 hr after administration. [26] It is important that the protective agent is present in renal tissue before damage occurs. This might explain why complete protection could not be observed when extract was given after injection of cisplatin.

Literature has shown Thespesia populnea contains flavonoids, tannins, terpenes, saponins and alkaloids such as quinines. In other nephroprotective medicinal plants, flavonoids have been reported to inhibit xenobiotic-induced nephrotoxicity in experimental animal models [27] due to their potent anti-oxidant or free radicals scavenging effects. [28] Alkaloids have also been reported to have antioxidant activity. In addition, flavonoids and saponins offer hepatoprotection. In accordance with these results, it may be hypothesized that the protection offered by the extract could have been due to the presence of flavonoids and alkaloids. Further work should focus on elucidating the actual protective mode of the extract.

 
 > References Top

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2.Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs.Nat Rev Drug Discov 2005;4:307-20.  Back to cited text no. 2
    
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20.Milbrodt M, Konig WA, Hausen BM. 7-hydroxy-2,3,5,6-tetrahydro-3,6,9-trimethylnaphtho [1,8-b,c] pyran-4,8-dione from Thespesia populnea. Phytochemistry 1997;45:1523-5.  Back to cited text no. 20
    
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24.Heidman HT, Gerkens JF, Jackson EK, Branch RA. Attenuation of cisplatin induced nephrotoxicity in the rat by high salt diet, furosemide and acetazolamide. Naunyn Schmiedebergs Arch Pharmacol 1985;329:201-5.  Back to cited text no. 24
    
25.Montine TJ, Borch RF. Role of endogenous sulfur containing nuclephiles in an in vitro model of cis-diamminedichloroplatinium(II)-induced nephrotoxicity. Biochem Pharmacol 1990;39:1751-7.  Back to cited text no. 25
    
26.Rao M, Rao MM. Protective effects of selenomethionine against cisplatin induced renal toxicity in mice and rats. J Pharm Pharmacol 1998;50:687-91.  Back to cited text no. 26
    
27.Devipriya S, Shyamaladevim CS. Protective effect of quercetin in cisplatin induced cell injury in the rat kidney. Indian J Pharmacol1999;31:422-6.  Back to cited text no. 27
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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