ORIGIN AL ARTI CLE
Effect of red maca(Lepidium meyenii)on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia
C.Gonzales,J.Leiva-Revilla,J.Rubio,M.Gasco&G.F.Gonzales
Department of Biological and Physiological Sciences,Faculty of Sciences and Philosophy and Instituto de Investigaciones de la Altura,Universidad Peruana Cayetano Heredia,Lima,Peru
Introduction
The growth of prostate gland is an androgen-dependent process in which testosterone(T)is converted,by5a-reducta action,to dyhydrotestosterone(DHT)that is the most active androgen involved in the regulation of prostate gland(Campbell et al.,2006).Benign prostatic hyperplasia (BPH)is a progressive and androgen-dependent dia characterized by a dysregulation of5a-reducta action (Bauman et al.,2006)which leads to higher prostatic levels of DHT and the increa in size of the prostate gland (Martinez Caballero et al.,2004;Petraki&Sfikas,2007). Previous studies have demonstrated that zinc is a mar-ker of prostate function(Wong et al.,2000;Yucra et al., 2006,20
GSIS
08).In this gland,higher values of zinc inhibit citrate oxidation in the Krebs cycle,allowing its accumu-lation as an end-product of metabolism rather than an utilizable intermediate of Krebs cycle(Costello et al., 2004;Costello&Franklin,2006).In BPH,incread levels of prostatic zinc are responsible for the impaired citrate oxidation obrved in this pathology(Habib et al.,1979; Costello&Franklin,2006;Sing et al.,2006).Also,it was reported that zinc regulates androgen metabolism(Abbasi et al.,1980;Wong et al.,2000)where high prostatic zinc levels obrved in BPH were associated with DHT/T ratio>1(Habib et al.,1979).
Finasteride(FN),a5a-reducta inhibitor,is one of the most ud drugs to induce androgen suppression in patients with BPH(Gao et al.,2004).5a-reducta blocks the conversion of T to DHT(Bartsch et al.,2002).How-ever,the cost burden associated with FN is substantial. For instance,its survival benefit is small and the effect is
Keywords
Preputial gland—prostate weight—prostatic zinc levels—red maca—minal vesicle
Correspondence
Johanna Leiva-Revilla,Department of Biological and Physiological Sciences,Faculty of Sciences and Philosophy and Instituto de Investigaciones de la Altura,Universidad Peruana Cayetano Heredia,PO Box1843, Lima,Peru.
Tel.:(+511)3190000ext.2515;
Fax:(+511)4821195;
E-mail:johanna.leiva@upch.pe
Accepted:March18,2011
doi:10.1111/j.1439-0272.2011.01190.x Summary
Lepidium meyenii(maca)is a plant that grows exclusively above4000m in the Peruvian central Andes.Red maca(RM)extract significantly reduced prostate size in rats with benign prostatic hyperplasia(BPH)induced by testosterone enanthate(TE).Zinc is an important regulator of prostate function.This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE.Also,the study attempted to determine the best marker for the effect of RM on x accessory glands.Rats treated with RM extract from day1 to day14reverd the effect of TE administ
ration on prostate weight and zinc levels.However,RM administered from day7to day14did not reduce the effect of TE on all studied variables.Finasteride(FN)reduced prostate,minal vesicle and preputial gland weights in rats treated with TE.Although RM and FN reduced prostate zinc levels,the greatest effect was obrved in TE-treated rats with RM from day1to day14.In addition,prostate weight and zinc levels showed the higher diagnosis values than preputial and minal vesicle weights. In conclusion,RM administered from day1to day14reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE.Also, this experimental model could be ud as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products bad on maca.
only realized after a long time period(Zeliadt et al., 2005).For such reasons,it would be helpful tofind alter-native strategies for the treatment of prostate dia. Accordingly,a arch for safer natural products has been undertaken(Talpur et al.,2003).
There is an association between the high glucosinolates content in cruciferous vegetables and its role in cancer prevention including different prostate pathologies(Tala-lay&Fahey,2001;Keum et al.,2005;Ray,2005;Steinbre-cher et al.,2009;Hwang&Lee,2010).Isothiocyanates, the biologically active breakdown products of glucosino-lates,prent chemoprotective activities(Chiao et al., 2004;H
wang&Lee,2010).In fact,plants from the genus Lepidium have been demonstrated to reduce prostate size and volume in castrated rats with prostatic hyperplasia induced by exogenous steroids(Martinez Caballero et al., 2004).
Lepidium meyenii(maca)is a plant that grows exclu-sively over4000m in the Peruvian central Andes(Valerio &Gonzales,2005).Maca is naturally prent in different varieties which are characterized by the external colour of their hypocotyls(Tello et al.,1992;Yllescas,1994).From the,red maca(RM)significantly reduced prostate size in rats with prostatic hyperplasia induced by testosterone enanthate(TE)(Gonzales et al.,2005,Gonzales et al., 2007;Gasco et al.,2007).In fact,RM reduced prostate weight in a do–respon manner without any changes in testosterone levels and minal vesicle weight(Gasco et al.,2007;Gonzales et al.,2007).However,it is still unknown whether RM is acting through prostatic zinc values.
Regarding the condary metabolites involved in the effect of RM on prostate size,when different dos of benzylglucosinolates in RM extracts were assd,a do-dependent reduction in prostate weight was obrved, suggesting that the compounds may be responsible for the biological effect of RM(Gonzales et al.,2007).How-ever,it was suggested that other condary metabolites prented in RM could be also responsible for the effect on prostate size(Gonzales et al.,
2007).Conquently, glucosinolates content should not be ud as a chemical marker to standardized products bad on maca.In fact, others authors found that polyphenols could inhibit pros-tate size(Ganapathy et al.,2010;Siddiqui et al.,2010). For instance,it was suggested that polyphenols in RM may be related to the reduction in prostate size(Gonzales et al.,2008).
The study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE.Also, this study attempted to determine the best marker for RM action in the x accessory glands asssing prostate, minal vesicles and preputial glands weights as well as prostate zinc levels.Materials and methods
Animals
Thirty-six male rats from a3-month-old Holtzman strain (359.32±6.86g)were obtained from the animal hou of the Universidad Peruana Cayetano Heredia(Lima,Peru). Rats were houd3–6per cage and maintained at22±1C with a12:12light/dark cycle.Rats were provided with Purina laboratory chow and tap water ad libitum.
All animal experiments were conducted in compliance with‘Guide of the care and u of laboratory animals’(National Rearch Council,1996).The Institutional Review Board of the Scientific Rearch
Office,Universi-dad Peruana Cayetano Heredia,approved the study. Design
Figure1shows aflow diagram to describe the experi-ments.In brief,rats were randomly divided in six differ-ent groups(n=6)according to the treatment:Group I: same oil(TE vehicle)+distilled water(RM vehicle) (control);Group II:TE+distilled water(TE);Group III: TE+RM extract from day1to day14of treatment (RMd1);Group IV:TE+FN from day1to day14of treatment(FNd1);Group V:TE+RM extract from day7 to day14of treatment(RMd7);Group VI:TE+FN from day7to day14of treatment(FNd7).
In groups2–6,rats were injected with0.1ml of TE (25mg)on day1and day7of treatment to induce a BPH state as previously reported(Gonzales et al.,2007). Sesame oil was ud as a vehicle for TE that was adminis-tered in the same way as explained for TE(on days1and 7of treatment).
On the other hand,RM extract(2g kg)1body weight per day)(Gonzales et al.,2005)or FN(0.1mg day)1) (Gonzales et al.,2007)was orally administered using an intubation needle No.18(Fisher Scientific,Pittsburgh, Pennsylvania).For RM and FN treatments,distilled water was ud as a vehicle.Before RM and FN treatments from day7to day14,rats in groups5(RMd7)and6(FNd7) received distilled water.
Acute administration of maca did not show any toxic effect in mice in dos up to16g kg)1(Valerio&
Gonzales,2005).In fact,long-term administration of maca did not have adver effects on different organ weights or histology(Chung et al.,2005;Gonzales et al., 2006;Gasco et al.,2007).
Preparation of aqueous extract of red maca
The red variety of the hypocotyls ii was obtained from Carhuamayo at4000m altitude in Junin,
C.Gonzales et al.RM effect on prostate zinc levels
Peru.The identity of the plant was authenticated in the Department of Pharmaceutical Sciences,Universidad Peruana Cayetano Heredia (voucher specimen:IFV 1885).Thereafter,100g of the dried pulverized hypocotyls was placed in a container with 600ml of water and boiled for 60min.The preparation was left standing to cool,filtered and freeze-dried.From this,1g of dried hypocotyls of RM produced 0.34g of freeze-dried RM.The freeze-dried extract was diluted further to obtain a solution equivalent to a do of 2g raw material kg )1body weight (Gonzales et al.,2005).Organ weights
Twenty-four hours after the last treatment,rats were killed and the following reproductive organs wer
e dis-cted out,cleaned of adhering connective tissues and accurately weighed:testes,epididymis,minal vesicle,preputial glands,and ventral prostate.Prostatic zinc levels
At the end of the experiment,rats were killed and pros-tates were discted out.The prostate were homogenized in 5.0ml of saline (NaCl 0.9%)and centrifuged at 3500g for 10min.The supernatant was obtained for zinc deter-mination by colorimetric assay (Gonzales,2007).All sam-ples were run in a same assay to avoid between-assay variation.Statistical analys
Data were analyd using the statistical package stata ver-sion 8.0for personal computer (Stata Corporation,
College Station,TX,USA).Kruskal–Wallis nonparametric test was ud to asss differences between groups.When results were statistically significant,Mann–Whitney U test was performed to asss differences between pair of groups.Data are prented as mean ±SEM.The area under receiver operating characteristic (ROC)curve was ud to measure the discriminatory ability of the variables assd (zinc levels in prostate and preputial glands,mi-nal vesicle,and prostate weights).In addition,nsitivity,specificity,positive predictive value (PPV)and negative predictive value (NPV)were determined for each variable.In general,P <0.05was considered statistically significant.
Results
Reproductive organ weights
No significance differences in testis and epididymis weights between groups (Data not shown).
Figures 2(a,b)and 3showed the effect of RM on mi-nal vesicle,preputial gland and prostate weights in rats treated with TE to induce prostatic hyperplasia.TE-treated rats showed an increa in minal vesicle (3.10±0.07g,media ±SEM),preputial gland (0.30±0.03g)and pros-tate (0.80±0.09g)weights when compared with control group (1.07±0.11,0.10±0.01and 0.43±0.03g respec-tively;P <0.05).
In rats treated with TE,RM administered from day 7(RMd7)was not able to reduce minal vesicle (3.39±0.11g),preputial gland (0.26±0.04g)and prostate (0.90±0.05)weights when compared with rats that received only TE (P >0.05).In fact,rats from RMd7group showed higher values than tho in control group (P <0.05).Seminal vesicle and preputial gland weights
in
Fig.1Diagram of the experimental design in this study.Distilled water and same oil are vehicles of red maca (RM)and testosterone enanthate respectively.Finasteride (FN)was also dissolved in distilled water.RM extract from day 1to day 14of treatment (RMd1)/FN from day 1to day 14of treatment (FNd1),RM (2g kg )1)or FN (0.1mg day )1)administered from day 1to 14;RMd7/FNd7,RM or FN administered from day 7to 14.
后羿的故事RM effect on prostate zinc levels C.Gonzales et al.
水洞0ffice
FNd7group(2.26±0.28g and0.17±0.01g respec-tively)showed intermediate values than rats in control and TE groups(P<0.05).A reduction in prostate weight (0.52±0.03g)was obrved in FNd7group when com-pared with TE-treated rats(P<0.05),reaching similar values than control group.
The administration of RM from day1(RMd1)reduced prostate weight(0.54±0.06g,P<0.05)in tho rats where prostatic hyperplasia was induced by TE.In addi-tion,the reduction obrved in prostate weight reached similar values than tho reported in control group.Red maca reverd the effect of TE on preputial gland weight (0.21±0.02g,P<0.05).Moreover,rats in RMd1group showed no differences in minal vesicle weight than tho rats treated with TE(3.15±0.10g,P>0.05).In FNd1 group,a reduction in minal vesicle(2.42±0.16g),
Groups
FNd1RMd7FNd7
FNd1RMd7FNd7
Groups
a,b,e业精于勤而荒于嬉
a,b
a
FNd1RMd7FNd7
a
b,c
b,c
正能量的故事
C.Gonzales et al.RM effect on prostate zinc levels
preputial gland(0.22±0.02g),and prostate(0.57±0.05g)weights was obrved with respect to TE-treated rats(P<0.05).
Prostate zinc levels
Testosterone enanthate administration significantly incread prostate zinc levels when compared with control rats(up to197.3%,P<0.05).In rats from RMd1,a reduction in prostate zinc levels was obs
erved when compared with TE-treated rats(up to55.8%,P<0.05), reaching similar values than tho from control group. Rats treated with FN for14days(FNd1)partially reverd the effect of TE showing intermediate values between TE-treated(a reduction through18.3%, P<0.05)and control(up to143.8%higher)rats (Fig.4a).In addition,correlation and regression analysis revealed a positive association between prostate weight and prostatic zinc levels(r=0.762and R2=0581; P<0.001)(Fig.4b).
Determination of diagnostic efficiency statistics Becau preputial gland,minal vesicle,prostate weights and prostate zinc levels showed statistical changes among treatments,the parameters were chon for the diagnos-tic analysis.Regarding the area under ROC curves,pros-tate weight(0.80)and prostate zinc levels(0.78)showed higher values than preputial gland(0.50)and minal ves-icle(0.65)weights.Diagnostic test for prostate weight was 62.5%for nsitivity,90.0%for specificity,75.0%for PPV and83.3%for NPV.In prostate zinc levels,diagnos-tic values were63.0%for nsitivity,90.0%for specificity, 84.0%for PPV and75.2%for NPV.
Discussion
扁担作字两头看打一成语Previously,we have demonstrated that RM showed the best
beneficial effect,when compared with yellow and black varieties,on prostate weight in normal and TE-treated rats (Gonzales,2006a;Gonzales et al.,2006).In the prent study,TE administration(total do of50mg)resulted in an increa in preputial gland,minal vesicle and prostate weights.In this study,RM administered from day1 reverd the effect of TE treatment in prostate weight with-out affecting minal vesicle weight;meanwhile,FN showed to reduce both prostate and minal vesicle weights.The results are in accordance with previous studies(Gasco et al.,2007;Gonzales et al.,2007).Although FN is an elec-tive drug for BPH(Tempany et al.,1993),it is associated with some side effects related to a reduced male and female xual tile dysfunction and diminished libido),gynecomastia and depression(Zlotta et al.,2005;Traish et al.,2011).Becau of this,RM could become an important alternative for the treatment of BPH.
Prostate zinc levels were incread by TE administra-tion,an experimental model to induce prostatic hyperpla-sia.The outcomes from the prent study revealed that RM was able to reduce zinc levels in TE-treated rats.As mentioned earlier,zinc avoids citrate oxidation to regu-late the proliferation of prostatic cells(Duncan,1984; Vallee,1988,1993).Also,other authors reported a rela-tion between the alteration in androgen metabolism and higher zinc levels in patients with BPH(Abbasi et al., 1980;Wong et al.,2000).In the prent study,a positive correlation was found between zinc and prost
ate weight that is in accordance with other studies where higher zinc levels are obrved in BPH(Costello&Franklin,2006;
FNd1
(b)
Fig.4Effect of red maca(RM)on prostate zinc levels in rats with prostatic hyperplasia induced by testosterone enanthate(a).Correla-
吹拂拼音prostate weight
expresd
versus testoster-
day1to
RM effect on prostate zinc levels C.Gonzales et al.
