Skip to main content
Top
Published in: Inflammopharmacology 5/2016

01-10-2016 | Original Article

Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion

Authors: Amita Verma, Prakash Chandra Bhatt, Gaurav kaithwas, Nikunj Sethi, Mohd Rashid, Yashwant Singh, Mahfoozur Rahman, Fahad Al-Abbasi, Firoz Anwar, Vikas Kumar

Published in: Inflammopharmacology | Issue 5/2016

Login to get access

Abstract

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC–MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (H2O2) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-β) and inflammatory mediator (PGE2). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC–MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.
Literature
go back to reference Abdel-Naim A, Abdel-Wahab M, Attia F (1999) Protective effects of vitamin E and probucol against gentamicin-induced nephrotoxicity in rats. Pharmacol Res 40:183CrossRefPubMed Abdel-Naim A, Abdel-Wahab M, Attia F (1999) Protective effects of vitamin E and probucol against gentamicin-induced nephrotoxicity in rats. Pharmacol Res 40:183CrossRefPubMed
go back to reference Afzal M, Kazmi I, Khan R, Singh R, Pravez M, Imam F, Anwar F (2013) Pharmacological evaluation of gatifloxacin in chemically induced hepatocarcinogenesis: a new tool for hepatocellularcarcinoma treatment. J Cancer Sci Ther 5:1CrossRef Afzal M, Kazmi I, Khan R, Singh R, Pravez M, Imam F, Anwar F (2013) Pharmacological evaluation of gatifloxacin in chemically induced hepatocarcinogenesis: a new tool for hepatocellularcarcinoma treatment. J Cancer Sci Ther 5:1CrossRef
go back to reference Anwar F, Al-Abbasi FA, Bhat PC, Ahmad A, Sethi N, Kumar V (2015a) Umbelliferone β-D-galactopyranoside inhibits chemically induced renal carcinogenesis via alteration of oxidative stress, hyperproliferation and inflammation: possible role of NF-κB. Toxicol Res 4:1308–1323CrossRef Anwar F, Al-Abbasi FA, Bhat PC, Ahmad A, Sethi N, Kumar V (2015a) Umbelliferone β-D-galactopyranoside inhibits chemically induced renal carcinogenesis via alteration of oxidative stress, hyperproliferation and inflammation: possible role of NF-κB. Toxicol Res 4:1308–1323CrossRef
go back to reference Anwar F, Mushtaq G, Kazmi I, Afzal M, Khan R, Al-Abbasi FA, Ahmad A, Kumar V (2015b) Anticancer effect of rosiglitazone in rats treated with Nnitrosodiethylamine via inhibition of DNA synthesis: an implication for hepatocellular carcinoma. RSC Adv 5:68385–68391CrossRef Anwar F, Mushtaq G, Kazmi I, Afzal M, Khan R, Al-Abbasi FA, Ahmad A, Kumar V (2015b) Anticancer effect of rosiglitazone in rats treated with Nnitrosodiethylamine via inhibition of DNA synthesis: an implication for hepatocellular carcinoma. RSC Adv 5:68385–68391CrossRef
go back to reference Athar M, Sharma SD, Iqbal M, Sultana S, Pandaya KB, Tripathi IP (1996) Coordination of copper polyamines complex with immidiozoles potentiates its superoxide dismutase mimicking activity and abolishes its interactions with albumin. Biochem Mol Biol Int 39:813–821PubMed Athar M, Sharma SD, Iqbal M, Sultana S, Pandaya KB, Tripathi IP (1996) Coordination of copper polyamines complex with immidiozoles potentiates its superoxide dismutase mimicking activity and abolishes its interactions with albumin. Biochem Mol Biol Int 39:813–821PubMed
go back to reference Bancroft J, Gamble M (2008) Theory and practice of histological technique, 4th edn. Churchill Livingston, New York, London, San Francisco, Tokyo Bancroft J, Gamble M (2008) Theory and practice of histological technique, 4th edn. Churchill Livingston, New York, London, San Francisco, Tokyo
go back to reference Bartech H, Heathen E, Melville C (1989) Carcinogenic nitrosamines: free radical aspects of their action. Free Radicals Biol Med 7(6):637–644CrossRef Bartech H, Heathen E, Melville C (1989) Carcinogenic nitrosamines: free radical aspects of their action. Free Radicals Biol Med 7(6):637–644CrossRef
go back to reference Begum Q, Noori S, Mahboob T (2011) Antioxidant effect of sodium selenite on thioacetamide-induced renal toxicity. Pak J Biochem Mol Biol 44(1):21–26 Begum Q, Noori S, Mahboob T (2011) Antioxidant effect of sodium selenite on thioacetamide-induced renal toxicity. Pak J Biochem Mol Biol 44(1):21–26
go back to reference Benson AM, Hunkalar MJ, Talalay P (1980) Increase of NADPH, quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity. Proc Natl Acad Sci USA 77(9):5216–5220CrossRefPubMedPubMedCentral Benson AM, Hunkalar MJ, Talalay P (1980) Increase of NADPH, quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity. Proc Natl Acad Sci USA 77(9):5216–5220CrossRefPubMedPubMedCentral
go back to reference Buege JA, Aust SD (1978) Microsomal lipid peroxidation, in methods in enzymology. In: Packer L (ed) vol 52. Academic Press, NJ, pp 302–310 Buege JA, Aust SD (1978) Microsomal lipid peroxidation, in methods in enzymology. In: Packer L (ed) vol 52. Academic Press, NJ, pp 302–310
go back to reference Choudhury MD, Nath D, Talukdar AD (2011) Antimicrobial activity of Melastoma malabathricum L. Biol Environ Sci 7(1):76–78 Choudhury MD, Nath D, Talukdar AD (2011) Antimicrobial activity of Melastoma malabathricum L. Biol Environ Sci 7(1):76–78
go back to reference Claiborne A (1985) Catalase activity, in CRC handbook of methods for oxygen radical research. In: Greenwald AR (ed). CRC Press, Boca Raton, pp 283–284 Claiborne A (1985) Catalase activity, in CRC handbook of methods for oxygen radical research. In: Greenwald AR (ed). CRC Press, Boca Raton, pp 283–284
go back to reference De Flora S, Ramel C (1998) Mechanisms of inhibitors of mutagenesis and carcinogenesis, classification and overview. Mutat Res 202:285–306CrossRef De Flora S, Ramel C (1998) Mechanisms of inhibitors of mutagenesis and carcinogenesis, classification and overview. Mutat Res 202:285–306CrossRef
go back to reference Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione-Stransferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139PubMed Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione-Stransferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139PubMed
go back to reference Iqbal Z, Akhtar MS, Sindhu Z, Khan MN, Jabbar A (2003) Herbal dewormers in livestock—a traditional therapy. Int J Agric Biol 5:199–206 Iqbal Z, Akhtar MS, Sindhu Z, Khan MN, Jabbar A (2003) Herbal dewormers in livestock—a traditional therapy. Int J Agric Biol 5:199–206
go back to reference Jollow DJ, Mitchell JR, Zampagilone N, Gillette JR (1974) Bromobenzene-induced liver necrosis: protective role of glutathione and evidence for 3,4-bromobenzene oxides as a hepatotoxic intermediate. Pharmacology 11:151–169CrossRefPubMed Jollow DJ, Mitchell JR, Zampagilone N, Gillette JR (1974) Bromobenzene-induced liver necrosis: protective role of glutathione and evidence for 3,4-bromobenzene oxides as a hepatotoxic intermediate. Pharmacology 11:151–169CrossRefPubMed
go back to reference Kanter MW (1975) Clinical chemistry. The Bobber Merill Company Inc, USA 80 Kanter MW (1975) Clinical chemistry. The Bobber Merill Company Inc, USA 80
go back to reference Kaur G, Lone IA, Ather M, Alam S (2007) Protective effect of Didymocarpus pedicellata on ferric nitrilotriacetate (Fe- NTA) induced renal oxidative stress and hyperproliferative response. Chem Biol Interact 165:33–44CrossRefPubMed Kaur G, Lone IA, Ather M, Alam S (2007) Protective effect of Didymocarpus pedicellata on ferric nitrilotriacetate (Fe- NTA) induced renal oxidative stress and hyperproliferative response. Chem Biol Interact 165:33–44CrossRefPubMed
go back to reference Khan N, Sultana S (2005) Chemomodulatory effect of Ficus racemosa extract against chemically induced renal carcinogenesis and oxidative damage response in Wistar rats. Life Sci 77:1194–1210CrossRefPubMed Khan N, Sultana S (2005) Chemomodulatory effect of Ficus racemosa extract against chemically induced renal carcinogenesis and oxidative damage response in Wistar rats. Life Sci 77:1194–1210CrossRefPubMed
go back to reference Khan R, Kazmi I, Afzal M, Al-Abbasi FA, Mushtaq G, Ahmad A, Kumar V, Anwar F (2015) Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino wistar rats. RSC Adv 5:67996–68002CrossRef Khan R, Kazmi I, Afzal M, Al-Abbasi FA, Mushtaq G, Ahmad A, Kumar V, Anwar F (2015) Fixed dose combination therapy loperamide and niacin ameliorates diethylnitrosamine-induced liver carcinogenesis in albino wistar rats. RSC Adv 5:67996–68002CrossRef
go back to reference Kornberg A (1995) Lactic dehydrogenase of muscle, in methods in enzymology. In: Colowick SP, Kaplan NO (eds), vol. I. Academic Press, New York, pp 441–443 Kornberg A (1995) Lactic dehydrogenase of muscle, in methods in enzymology. In: Colowick SP, Kaplan NO (eds), vol. I. Academic Press, New York, pp 441–443
go back to reference Kumar V, Ahmed D, Anwar F, Ali M, Mujeeb M (2013a) Enhanced glycemic control, pancreas protective, antioxidant and hepatoprotective effects by umbelliferon-α-D-glucopyranosyl-(2I→1II)-α-D-glucopyranoside in streptozotocin induced diabetic rats. Springer Plus 2:639CrossRefPubMedPubMedCentral Kumar V, Ahmed D, Anwar F, Ali M, Mujeeb M (2013a) Enhanced glycemic control, pancreas protective, antioxidant and hepatoprotective effects by umbelliferon-α-D-glucopyranosyl-(2I→1II)-α-D-glucopyranoside in streptozotocin induced diabetic rats. Springer Plus 2:639CrossRefPubMedPubMedCentral
go back to reference Kumar V, Ahmed D, Gupta PS, Anwar F, Mujeeb M (2013b) Anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of Melastoma malabathricum Linn. leaves in streptozotocin induced diabetic rats. BMC Complement Altern Med 13:222CrossRefPubMedPubMedCentral Kumar V, Ahmed D, Gupta PS, Anwar F, Mujeeb M (2013b) Anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of Melastoma malabathricum Linn. leaves in streptozotocin induced diabetic rats. BMC Complement Altern Med 13:222CrossRefPubMedPubMedCentral
go back to reference Kumar V, Al-Abbasi FA, Ahmed D, Verma A, Mujeeb M, Anwar F (2015) Paederia foetida Linn. inhibits adjuvant induced arthritis by suppression of PGE2 and COX-2 expression via nuclear factor-κB. Food Funct 6:1652–1666CrossRefPubMed Kumar V, Al-Abbasi FA, Ahmed D, Verma A, Mujeeb M, Anwar F (2015) Paederia foetida Linn. inhibits adjuvant induced arthritis by suppression of PGE2 and COX-2 expression via nuclear factor-κB. Food Funct 6:1652–1666CrossRefPubMed
go back to reference Kumar V, Yadav PS, Singh UP, Bhat HR, Rana A, Zaman K (2010) Pharmacognostical evaluation of Cuscuta reflexa Roxb. Phcog J 2(6):74–82 Kumar V, Yadav PS, Singh UP, Bhat HR, Rana A, Zaman K (2010) Pharmacognostical evaluation of Cuscuta reflexa Roxb. Phcog J 2(6):74–82
go back to reference Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474CrossRefPubMed Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474CrossRefPubMed
go back to reference Nazlina I, Norha S, Zarina AW, Ahmad IB (2008) Cytotoxicity and antiviral activity of Melastoma malabathricum extracts. Malays Appl Biol 37(2):53–55 Nazlina I, Norha S, Zarina AW, Ahmad IB (2008) Cytotoxicity and antiviral activity of Melastoma malabathricum extracts. Malays Appl Biol 37(2):53–55
go back to reference Oduola TI, Bello G, Adeosun A, Abdul-Waheed G, Raheem Avwioro G (2010) Hepatotoxicity and nephrotoxicity evaluation in Wistar albino rats exposed to Morinda lucida leaf extract. North Am J Med Sci 2:230–233 Oduola TI, Bello G, Adeosun A, Abdul-Waheed G, Raheem Avwioro G (2010) Hepatotoxicity and nephrotoxicity evaluation in Wistar albino rats exposed to Morinda lucida leaf extract. North Am J Med Sci 2:230–233
go back to reference Orlowski M, Meister A (1973) g-Glutamyl cyclotransferase distribution, isozymic forms and specificity. J Biol Chem 248:2836–2844PubMed Orlowski M, Meister A (1973) g-Glutamyl cyclotransferase distribution, isozymic forms and specificity. J Biol Chem 248:2836–2844PubMed
go back to reference Perchellet JP, Perchellet EM, Orten DK, Schneider BA (1985) Inhibition of the effects of 12-O-tetradecanoylphorbol-13-acetate on mouse epidermal glutathione peroxidase and ornithine decarboxylase activities by glutathione level-raising agents and selenium containing compounds. Cancer Lett 26(3):283–293CrossRefPubMed Perchellet JP, Perchellet EM, Orten DK, Schneider BA (1985) Inhibition of the effects of 12-O-tetradecanoylphorbol-13-acetate on mouse epidermal glutathione peroxidase and ornithine decarboxylase activities by glutathione level-raising agents and selenium containing compounds. Cancer Lett 26(3):283–293CrossRefPubMed
go back to reference Pick A, Keisari Y (1981) Superoxide anion and H2O2 production by chemically elicited peritoneal macrophages— induction by multiple non phagocytic stimulus. Cell Immunol 59:301–308CrossRefPubMed Pick A, Keisari Y (1981) Superoxide anion and H2O2 production by chemically elicited peritoneal macrophages— induction by multiple non phagocytic stimulus. Cell Immunol 59:301–308CrossRefPubMed
go back to reference Pracheta P, Sharma V, Singh L, Paliwal R, Sharma S, Yadav S, Sharma S (2011) Chemopreventive effect of hydroethanolic extract of Euphorbia neriifolia leaves against DENA-induced renal carcinogenesis in mice. Asian Pac J Cancer Prev 12(3):677–683PubMed Pracheta P, Sharma V, Singh L, Paliwal R, Sharma S, Yadav S, Sharma S (2011) Chemopreventive effect of hydroethanolic extract of Euphorbia neriifolia leaves against DENA-induced renal carcinogenesis in mice. Asian Pac J Cancer Prev 12(3):677–683PubMed
go back to reference Rehman MU, Tahir M, Khan AQ, Khan R, Lateef A, Hamiza OO, Qamar W, Ali F, Sultana F (2013) Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: plausible role of NF-kB. Toxicol Lett 216:146–158CrossRefPubMed Rehman MU, Tahir M, Khan AQ, Khan R, Lateef A, Hamiza OO, Qamar W, Ali F, Sultana F (2013) Chrysin suppresses renal carcinogenesis via amelioration of hyperproliferation, oxidative stress and inflammation: plausible role of NF-kB. Toxicol Lett 216:146–158CrossRefPubMed
go back to reference Shaheen NEM (2013) Oxidative stress of diethylnitrosamine on the functions of kidney in male rats and effective role of rutin and/or selenium. J Appl Sci Res 9(13):6684–6691 Shaheen NEM (2013) Oxidative stress of diethylnitrosamine on the functions of kidney in male rats and effective role of rutin and/or selenium. J Appl Sci Res 9(13):6684–6691
go back to reference Sirat HM, Susanti DM, Ahmad F, Takayama H, Kitajima M (2010) Amides, triterpene and flavonoids from the leaves of Melastoma malabathricum L. J Nat Med 64:492–495CrossRefPubMed Sirat HM, Susanti DM, Ahmad F, Takayama H, Kitajima M (2010) Amides, triterpene and flavonoids from the leaves of Melastoma malabathricum L. J Nat Med 64:492–495CrossRefPubMed
go back to reference Solanki V, Rana RS, Slaga TJ (1981) Diminution of mouse epidermal superoxide dismutase and catalase activity by tumor promoter. Carcinogenesis 2:1141–1146CrossRefPubMed Solanki V, Rana RS, Slaga TJ (1981) Diminution of mouse epidermal superoxide dismutase and catalase activity by tumor promoter. Carcinogenesis 2:1141–1146CrossRefPubMed
go back to reference Sun Y (1980) Free radicals, antioxidant enzymes, and carcinogenesis. Free Radical Biol Med 8:583–599CrossRef Sun Y (1980) Free radicals, antioxidant enzymes, and carcinogenesis. Free Radical Biol Med 8:583–599CrossRef
go back to reference Susantia D, Sirata HM, Ahmada F, Alib RM, Aimic N, Kitajimac M (2007) Antioxidant and cytotoxic flavonoids from the flowers of Melastoma malabathricum L. Food Chem 103(3):710–716CrossRef Susantia D, Sirata HM, Ahmada F, Alib RM, Aimic N, Kitajimac M (2007) Antioxidant and cytotoxic flavonoids from the flowers of Melastoma malabathricum L. Food Chem 103(3):710–716CrossRef
go back to reference Talalay P, Fahey JW, Holtzclaw WD, Prestera T, Zhang Y (1995) Chemoprotection against cancer by phase 2 enzyme induction. Toxicol Lett 82–83:173–179CrossRefPubMed Talalay P, Fahey JW, Holtzclaw WD, Prestera T, Zhang Y (1995) Chemoprotection against cancer by phase 2 enzyme induction. Toxicol Lett 82–83:173–179CrossRefPubMed
go back to reference Zakaria ZA, Nor RNSRM, Hanan Kumar G, Ghani ZDFA, Sulaiman MR (2011) Antinociceptive, anti-inflammatory and antipyretic properties of Melastoma malabathricum leaves aqueous extract in experimental animals. Can J Physiol Pharmacol 84:1291–1299CrossRef Zakaria ZA, Nor RNSRM, Hanan Kumar G, Ghani ZDFA, Sulaiman MR (2011) Antinociceptive, anti-inflammatory and antipyretic properties of Melastoma malabathricum leaves aqueous extract in experimental animals. Can J Physiol Pharmacol 84:1291–1299CrossRef
go back to reference Zakaria ZA, Rofiee MS, Mohamed AM, The LK, Salleh MZ (2010) In vitro Antiproliferative and antioxidant activities and total phenolic contents of the extracts of Melastoma malabathricum leaves. J Acupuncture Meridian Stud 4(4):248–256CrossRef Zakaria ZA, Rofiee MS, Mohamed AM, The LK, Salleh MZ (2010) In vitro Antiproliferative and antioxidant activities and total phenolic contents of the extracts of Melastoma malabathricum leaves. J Acupuncture Meridian Stud 4(4):248–256CrossRef
Metadata
Title
Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion
Authors
Amita Verma
Prakash Chandra Bhatt
Gaurav kaithwas
Nikunj Sethi
Mohd Rashid
Yashwant Singh
Mahfoozur Rahman
Fahad Al-Abbasi
Firoz Anwar
Vikas Kumar
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 5/2016
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-016-0276-1

Other articles of this Issue 5/2016

Inflammopharmacology 5/2016 Go to the issue