Force Required to Cinch the Tricuspid Annulus: An Ex-Vivo Study.

BACKGROUND AND AIM OF THE STUDY: Tricuspid annuloplasty is the most preferred technique for the treatment of functional tricuspid regurgitation (FTR). However, high incidences of recurrent regurgitation and risky reoperation demands a deeper insight into the technique. The cinching force required to bring a dilated annulus back to the original size is unknown. The study aim was to quantify the cinching force in the tricuspid annulus which can contribute to the long-term durability of tricuspid annuloplasty and percutaneous device design. METHODS: In ten ovine hearts, a suture was anchored around the free wall of the tricuspid annulus with the free end attached to a force transducer. The force transducer was mounted on a slider system which pulled the suture at regular intervals. Closure of the tricuspid valve was achieved by pressurizing the right ventricle at 30 mmHg through the pulmonary valve. The suture was pulled to cinch the tricuspid annulus. The tricuspid annulus area was measured from images taken at each increment, and the corresponding force was recorded. The hearts were tested for three conditions: (i) non-pressurized (NP); (ii) pressurized (P; normal), and (iii) dilated-pressurized (DP; diseased). Leakage data were also collected for pressurized and dilated pressurized conditions. Annulus dilation was created by injecting phenol into the annulus. RESULTS: The maximum annulus dilation obtained was 8.82%, and the maximum cinching force was 0.38 +/- 0.09 N. Leakage was increased by 81.73% from the pressurized to dilated condition. CONCLUSION: The minimal force required to cinch a tricuspid annulus with severe FTR (23.98% dilation) can be approximated to 0.25 N. The required cinching force can play a major role in the long-term durability of the tricuspid annuloplasty.

In vivo and in vitro antileishmanial activity of Bungarus caeruleus snake venom through alteration of immunomodulatory activity.

Leishmaniasis threatens more than 350 million people worldwide specially in tropical and subtropical region. Antileishmanial drugs that are currently available have various limitations. The search of new drugs from natural products (plants, animals) possessing antileishmanial activity is ventured throughout the world. The present study deals with the antileishmanial activity of Bungarus caeruleus snake venom (BCV) on in vitro promastigotes and amastigotes of Leishmania donovani parasite and leishmania infected BALB/c mice. The effect of BCV on peritoneal macrophage, release of cytokines from the activated macrophages, production of nitric oxide, reactive oxygen species and cytokines were studied in vivo and in vitro. IC50 value of BCV on L. donovani promastigote was 14.5 µg/ml and intracellular amastigote was 11.2 µg/ml. It activated peritoneal macrophages, significantly increased cytokines and interleukin production. BCV (20 µg/kg and 40 µg/kg body weight of mice) decreased parasite count by 54.9% and 74.2% in spleen and 41.4% and 60.4% in liver of infected BALB/c mice. BCV treatment significantly increased production of TNF-α, IFN-γ, ROS, NO in infected mice. Histological studies showed decreased granuloma formation in treated liver as compared with control. Liver and spleen structure was partially restored due to BCV treatment in infected mice. The present study revealed that BCV possessed antileishmanial activity against L. donovani parasite in vivo and in vitro and this activity was partly mediated through immunomodulatory activity involving macrophages.

Inhibition of toxic actions of phospholipase A2 isolated & characterized from the Indian Banded Krait (Bungarus fasciatus) venom by synthetic herbal compounds.

BACKGROUND & OBJECTIVES: Phospholipase A2 (PLA2 ) is one of the major constituents of krait venom associated with several pathophysiological actions like myotoxicity, cardiotoxicity, neurotoxicity, etc. As there was no specific antiserum available against Bungarus fasciatus venom, this study was done with synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum to neutralize the PLA2 induced toxicities in experimental models. METHODS: B. fasciatus venom phospholipase A2 fraction 38 (BF-38) was isolated by ion exchange chromatography, molecular weight was determined by mass spectrometry and its N terminal amino acid sequence was identified. Monospecific rabbit antiserum was raised against the PLA2 in presence of Freund complete adjuvant. The neutralization of PLA2 induced toxicities was done in in vitro and in in vivo models using synthetic herbal compounds, anti PLA2 rabbit antiserum and commercial polyvalent snake venom antiserum. RESULTS: A toxic PLA2 (BF-38) was purified from the B. fasciatus venom by CM-cellulose and HPLC, of 13.17 kDa and a minor band of 7.3 kDa using ESI-MS. The 13.17 kDa PLA2 sequence was NLYQFKNMIQC. The 7.3 kDa toxin sequence was RKCLTKYSQDNES and was found to be <10 per cent w/w. Anti PLA2 rabbit antiserum produced faint precipitant band in immunogel diffusion and showed low titre value. The commercial polyvalent snake venom antiserum, anti PLA2 rabbit antiserum and the synthetic herbal compounds neutralized the PLA2 induced toxicities at different intensities. INTERPRETATION & CONCLUSIONS: Our results suggested that synthetic herbal compound (BA) along with antiserum might provide effective protection against PLA2 induced toxicities of B. fasciatus venom.

Ethno biological usage of zoo products in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune disorder which causes swelling, redness, pain, stiffness, restriction of limb movements, decreases life expectancy and early death of the patients. Available drugs include non steroidal anti-inflammatory and analgesics, disease modifying anti-rheumatic drugs and steroids (glucocorticoids etc). All these drugs have their own limitations such as gastrointestinal irritations, cardiovascular problems, and drug dependency. Search for alternative therapy from natural products are being ventured throughout the world. Zoo therapy in arthritis, a common practice of the ancient times that have been mentioned in traditional and folk medicine. The scientific basis of some of the zoo products are being explored and have been showing promising results in experimental rheumatoid arthritis. These therapies have minimum side effects and many of them have potential to give rise to drug development clues against rheumatoid arthritis. The present review is an effort to establish the folk and traditional treatment of rheumatoid arthritis using zoo products.

Tricuspid annulus cinching force under pulmonary hypertensive right ventricle conditions: An ex vivo study.

This study investigates the force required to reduce or "cinch" the tricuspid annulus under elevated right ventricular pressures, commonly seen in patients with pulmonary hypertension. Tricuspid regurgitation affects 1.6 million Americans. Approximately 43% of patients who undergo tricuspid valve repair to correct tricuspid regurgitation will develop residual pulmonary hypertension, putting them at risk for developing increased right ventricle pressures. Previous studies have quantified the forces required to cinch the tricuspid annulus by only pressurizing the right ventricle, leaving out forces from the pressurized left ventricle and septal wall unaccounted for. This study pressurized both left and right ventricles of 10 porcine hearts to their normal physiological pressures of 110 mmHg and 30 mmHg respectively, then increased right ventricular pressures to mimic moderate and severe pulmonary hypertension. A suture was anchored around the free wall of the tricuspid annulus with the free end attached to a force transducer. The force transducer was mounted on a slider system which pulled the suture at regular intervals. The cinching force on the tricuspid annulus was quantified with each annular reduction by simulating peak systole condition in both ventricles. The data was compared with only the right ventricle pressurized as previous studies did. There were significant differences in required cinching forces with each increase in right ventricular pressure and between trials that pressurized both ventricles versus only the right ventricle, suggesting adoption of this physiologically improved protocol. We also found with increased cinching of the tricuspid annulus, notable changes occur in the mitral annulus.

Mitral valve annulus tension and the mechanism of annular dilation: an in-vitro study.

BACKGROUND AND AIM OF THE STUDY: The mitral annulus mechanics associated with annular dilation in pathologies such as mitral valve (MV) prolapse, ischemic and dilative heart diseases remain unknown. The study aim was to investigate annulus tension (AT) in the dilated annulus and in the displaced papillary muscles due to these pathological conditions. METHODS: Ten porcine MVs were harvested and mounted on a MV closure test rig with the papillary muscles held in the slack, normal, and taut positions. The MV annulus tissue rested on top of a plastic ring on which it could slide freely. The annulus was held by strings in the periphery during valve closure under hydrostatic trans-mitral pressure. The string tensions were measured, and further divided by string spacing to obtain the AT. Three annuli of normal, 25% dilated and 50% dilated annulus sizes were used. RESULTS: The AT was lowest at the commissural segment of the annulus, but increased towards the anterior and posterior segments, with a greater increase towards the anterior segment than towards the posterior. The AT increased with the increase of the apical PM displacement from the slack to normal, and then taut position in the commissural segment of the annulus. Although the AT increased with annulus area, the increase was less pronounced in the commissural segment than in the anterior and posterior segments. CONCLUSION: There is a significant difference in AT values between a normal and prolapsed MV, and between a normal MV and a MV with displaced papillary muscles. This difference suggests that annular dilation is a consequence and MV counteraction of imbalanced annular mechanics between the AT and myocardial force.

Herbs and herbal constituents active against snake bite.

Snake bite, a major socio-medical problem of south east asian countries is still depending on the usage of antisera as the one and only source of treatment, which has its own limitations. In India, mostly in rural areas, health centres are inadequate and the snake bite victims mostly depend on traditional healers and herbal antidotes, as an alternative treatment. The present review has been focussed on the varied folk and traditional herbs and their antisnake venom compounds, which might be a stepping stone in establishing the future therapy against snake bite treatment and management.

Role of annulus tension in annular dilatation.

BACKGROUND AND AIM OF THE STUDY: Mitral annulus mechanics are related to annular dilatation, and are not well understood. The study aim was to develop a method to measure regional annulus tension (AT) during valve closure, and to understand its role in annular dilatation. METHODS: A porcine mitral valve was harvested and mounted on a mitral valve closure test rig with the papillary muscles held in the normal position. The mitral valve annulus tissue rested on a plastic ring on which it was able to slide freely, there being no restriction in the interface between the annulus and the ring. The annulus was pulled by strings in the periphery during valve closure under a hydrostatic trans-mitral pressure. The string tensions were measured and further divided by string spacing to obtain the AT. A total of 10 mitral valves was tested. RESULTS: The AT distribution along the anterolateral annulus exhibited a concave curve. The anterior, commissural and posterior ATs were 40.0, 17.8, and 30.6 N/m, respectively, and the trans-mitral pressure 120 mmHg. The ATs in the three sections of the annulus were significantly different. CONCLUSION: A novel method to measure AT has been developed successfully. The AT was lower in the commissural section of the annulus than in the anterior or posterior sections. This finding may suggest that the potential for annular dilatation in the commissural section is high.

In vitro stretches of the mitral valve anterior leaflet under edge-to-edge repair condition.

Mitral valve edge-to-edge repair (ETER) alters valve mechanics, which may impact efficacy and durability of the repair. The objective of this paper was to quantify stretches in the central region of the anterior leaflet of the mitral valve after ETER with a single suture and 6 mm suture. Sixteen markers, forming a 4x4 array, were attached onto the central region of the mitral valve anterior leaflet. The mitral valve was subjected to ETER with a single suture and 6 mm suture, and mounted in an in vitro flow loop simulating physiological conditions. Images of the marker array were used to calculate marker displacement and stretch. A total of 9 mitral valves were tested. Two peak stretches were observed during a cardiac cycle, one in systole and the other in diastole under mitral valve edge-to-edge repair condition. The major principal (radial) stretch during systole was significantly greater than that during diastole. However, there was no significant difference between the minor principal (circumferential) stretch during diastole and that during systole. In addition, there were no significant differences in the radial and circumferential, or areal stretches and stretch rates during diastole between the single suture and 6 mm suture. The ETER subjects the mitral valve leaflets to double frequency of loading and unloading. Minor change in suture length may not result in a significant load difference in the central region of the anterior leaflet during diastole.

Papillary muscle and annulus size effect on anterior and posterior annulus tension of the mitral valve: an insight into annulus dilatation.

Mitral valve (MV) annulus mechanics and its effect on annulus dilatation are not well understood. The objective of the current study was to understand annulus tension (AT) during valve closure. A porcine MV rested on top of annulus rings with papillary muscles (PMs) held at slack, normal and taut conditions. The annulus was held by strings in the periphery during valve closure under static trans-mitral pressures. String tensions were measured and further used to calculate the anterior and posterior ATs. Three rings of different sizes were used to simulate normal and dilatated annuli. Fourteen MVs were tested. The anterior ATs were 37.21+/-11.03, 53.86+/-14.98 and 58.87+/-15.72N/m, respectively, at the slack, normal and taut PM positions in the normal annulus at the trans-mitral pressure of 16.3kPa (122mmHg). The posterior ATs were 24.52+/-5.68, 36.29+/-8.89 and 42.32+/-11.82N/m, respectively, at the slack, normal and taut PM positions in the normal annulus at the trans-mitral pressure of 16.3kPa (122mmHg). AT increased as the PM changed from slack to normal, then to taut PM positions. The AT increases with the increase of annulus area and linearly with the increase of trans-mitral pressure. The AT increases with the increases of apical PM displacement and dilatated annulus area, and reduces the potential of annulus dilatation. Low trans-mitral pressure due to existent mitral regurgitation, and MV prolapse increase the potential of annulus dilatation.

Therapeutic potential of krait venom.

Kraits belong to Elapideae and are widely distributed in East and South-East Asian countries. Krait venom possesses neurotoxins, membrane toxins, cardiotoxins, three finger toxins, metalloproteinases, cholinesterases, L-amino acid oxidases and serine proteases. The therapeutic potential of krait venom in pathophysiological conditions such as microbial and parasitic infections, cancer, arthritis, inflammation and blood coagulation disorder is discussed in this review. More intensive new research ventures are required to establish the therapeutic potential of krait venom in complex and emerging diseases.

Effects of Cinching Force on the Tricuspid Annulus: A Species Comparison.

PURPOSE: Tricuspid annuloplasty rings are commonly used to cinch an enlarged tricuspid annulus back to its original shape and size in patients with severe functional tricuspid regurgitation. However, the invasive operation is contraindicated for patients at risk for reoperation. Fortunately, transcatheter repair procedures, currently in the development process, are minimally invasive alternatives to current repair techniques. This study aims to determine the species-dependence of cinching force with the potential of informing transcatheter repair design by quantifying the minimum required cinching force necessary to reduce tricuspid regurgitation. METHODS: The cinching force necessary to reduce the septal-lateral diameter of a dilated annuls was quantified and compared in ten ovine hearts and nine porcine hearts. Additionally, a deparaffinization protocol and Verhoeff-Van Gieson stain were used to compare the microscopic structure of tissue samples at different stages of the experimental procedure in the two species. RESULTS: The maximum annulus dilation observed for the porcine was 11.2%, and the maximum cinching force was 0.40 ± 0.12 N. As previously demonstrated, ovine hearts yielded a maximum annulus dilation and cinching force of 8.82% and 0.38 ± 0.09 N respectively. Histological stains revealed no gross tissue differences between ovine and porcine septal or free wall tissues. CONCLUSION: The cinching force was not species dependent between ovine and porcine models. This study is an essential first step for determining which animal model should be utilized for the development of transcatheter devices.

Adipose Recruitment and Activation of Plasmacytoid Dendritic Cells Fuel Metaflammation.

In obese individuals, visceral adipose tissue (VAT) is the seat of chronic low-grade inflammation (metaflammation), but the mechanistic link between increased adiposity and metaflammation largely remains unclear. In obese individuals, deregulation of a specific adipokine, chemerin, contributes to innate initiation of metaflammation by recruiting circulating plasmacytoid dendritic cells (pDCs) into VAT through chemokine-like receptor 1 (CMKLR1). Adipose tissue-derived high-mobility group B1 (HMGB1) protein activates Toll-like receptor 9 (TLR9) in the adipose-recruited pDCs by transporting extracellular DNA through receptor for advanced glycation end products (RAGE) and induces production of type I interferons (IFNs). Type I IFNs in turn help in proinflammatory polarization of adipose-resident macrophages. IFN signature gene expression in VAT correlates with both adipose tissue and systemic insulin resistance (IR) in obese individuals, which is represented by ADIPO-IR and HOMA2-IR, respectively, and defines two subgroups with different susceptibility to IR. Thus, this study reveals a pathway that drives adipose tissue inflammation and consequent IR in obesity.

Mechanics of mitral valve edge-to-edge-repair and MitraClip procedure.

The edge-to-edge repair (ETER) technique has been used as a stand-alone procedure, or as a secondary procedure with ring annuloplasty for degenerative, functional mitral regurgitation, or for mitral regurgitation of other kinds of valvular etiologies. The percutaneous MitraClip technique based on ETER has been used in patients who are inoperable or at high surgical risk. However, adverse events such as residual mitral regurgitation, and clip detachment or fracture indicate that the mechanics underlying these procedures is not well understood. Therefore, current studies on mitral valve functionality and mechanics related to the ETER and MitraClip procedures are reviewed to improve the efficacy and safety of both procedures. Extensive in vivo, in vitro, and in silico studies related to ETER and MitraClip procedures along with MitraClip clinical trial results are presented and discussed herein. The ETER suture force and the mitral valve tissue mechanics and hemodynamics of each procedure are discussed. A quantitative understanding of the interplay of mitral valve components and as to biological response to the procedures remains challenging. Based on mitral valve mechanics, ETER or MitraClip therapy can be optimized to enhance repair efficacy and durability.

Tension to passively cinch the mitral annulus through coronary sinus access: an ex vivo study in ovine model.

INTRODUCTION: The transcatheter mitral valve repair (TMVR) technique utilizes a stent to cinch a segment of the mitral annulus (MA) and reduces mitral regurgitation. The cinching mechanism results in reduction of the septal-lateral distance. However, the mechanism has not been characterized completely. In this study, a method was developed to quantify the relation between cinching tension and MA area in an ex vivo ovine model. METHOD: The cinching tension was measured from a suture inserted within the coronary sinus (CS) vessel with one end tied to the distal end of the vessel and the other end exited to the CS ostium where it was attached to a force transducer on a linear stage. The cinching tension, MA area, septal-lateral (S-L) and commissure-commissure (C-C) diameters and leakage was simultaneously measured in normal and dilated condition, under a hydrostatic left ventricular pressure of 90 mm Hg. RESULTS: The MA area was increased up to 22.8% after MA dilation. A mean tension of 2.1 ± 0.5 N reduced the MA area by 21.3 ± 5.6% and S-L diameter by 24.2 ± 5.3%. Thus, leakage was improved by 51.7 ± 16.2% following restoration of normal MA geometry. CONCLUSION: The cinching tension generated by the suture acts as a compensation force in MA reduction, implying the maximum tension needed to be generated by annuloplasty device to restore normal annular size. The relationship between cinching tension and the corresponding MA geometry will contribute to the development of future TMVR devices and understanding of myocardial contraction function.

Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom.

A cytotoxin NN-32 (6.7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay. NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis. Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell. Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities.

A cytotoxic protein (BF-CT1) purified from Bungarus fasciatus venom acts through apoptosis, modulation of PI3K/AKT, MAPKinase pathway and cell cycle regulation.

BF-CT1, a 13 kDa protein isolated from Bungarus fasciatus snake venom through CM cellulose ion exchange chromatography at 0.02 M NaCl salt gradient showed cytotoxicity in in vitro and in vivo experimental models. In in vivo Ehrlich ascites carcinoma (EAC) induced BALB/c mice model, BF-CT1 treatment reduced EAC cell count significantly through apoptotic cell death pathway as evidenced by FACS analysis, increased caspase 3, 9 activity and altered pro, antiapoptotic protein expression. BF-CT1 treatment caused cell shrinkage, chromatin condensation and induced apoptosis through increased caspase 3, caspase 9 activity, PARP cleavage and down regulation of heat shock proteins in U937 leukemic cell line. Cytosolic cytochrome C production was increased after BF-CT1 treatment upon U937 cell line. BF-CT1 treated U937 cell showed cell cycle arrest at sub G1 phase through cyclin D and CDK down regulation with up regulation of p15 and p16. It also down regulated PI3K/AKT pathway and MAPkinase pathway and promoted apoptosis and regulated cell proliferation in U937 cells. BF-CT1 prevented angiogenesis in in vitro U937 cell line through decreased VEGF and TGF-ß1 production.

Annulus tension of the prolapsed mitral valve corrected by edge-to-edge repair.

BACKGROUND: Mitral valve (MV) performance after edge-to-edge repair (ETER) without ring annuloplasty is suboptimal. ETER efficacy needs to be evaluated from annulus tension (AT) of a prolapsed MV corrected by ETER to understand annular dilatation. METHODS: Ten porcine MVs were harvested and mounted on a MV closure test rig. The MV annulus tissue rested on top of a saddle-shaped plastic ring on which the annulus could slide freely. The annulus was held by strings in the periphery during MV closure under a hydrostatic trans-mitral pressure. String tensions were measured and further divided by string spacing to obtain AT. The MVs were then prolapsed by shifting split papillary muscles to simulate mono-leaflet prolapse due to elongation of chords, which insert into a single leaflet. Last, MV prolapse was corrected by ETER applied in the central leaflet region and AT was measured. RESULTS: AT in both anterior and posterior leaflet prolapse corrected by ETER was less than that of normal MVs. AT in the anterior leaflet prolapse corrected by ETER was less than that in the posterior leaflet prolapse corrected by ETER. CONCLUSION: ETER does not restore the normal AT and therefore leads potential of annular dilatation. The anterior leaflet prolapse has a greater potential of annular dilatation than the posterior leaflet prolapse after ETER. Annuloplasty is recommended to maintain long-term ETER efficacy.

Hepatoprotective activity of the edible snail (Bellamia bengalensis) flesh extract in carbon tetrachloride induced hepatotoxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In the folk-traditional medicine, snails were used to purify blood, boost immune system, prevent conjunctivitis and to treat liver problems. OBJECTIVES: To evaluate the hepatoprotective activity of the edible snail (Bellamia bengalensis) flesh extract in male Wistar rats treated with carbon tetrachloride as an hepatotoxicant. MATERIALS AND METHODS: Live adult Bellamia bengalensis was collected commercially from the Kolkata market. Aqueous flesh extract (BBE) was prepared in 0.9% saline and expressed in terms of wet weight basis. The aqueous flesh extract was administered orally (1, 2 g kg(-1)day(-1)) to male rats for 12 days. Liv52 was used as positive control. 24h after administration of extract, the rats were given a single oral dose of CCl(4) (1.25 ml kg(-1)), except vehicle control rats. After 24h of CCl(4) administration, all the animals were sacrificed to collect the blood and liver tissue. RESULTS: BBE (1 and 2 g kg(-1)day(-1), p.o.×12 days) significantly prevented CCl(4) induced elevation of SGOT, SGPT, γGT, ACP, ALP, bilirubin, LDH and CCl(4) induced decrease in total protein, triglyceride level in male Wistar rats. BBE treated rat liver anti-oxidant parameters (LPO, SOD, GSH, CAT, GPx) were significantly antagonized for the pro-oxidant effect of CCl(4). Histopathological studies also supported the protective effect of BBE. CONCLUSION: This study validated the folk and traditional use of snail in liver disorder through CCl(4)-induced rat experimental model.

Cytotoxic and antioxidant property of a purified fraction (NN-32) of Indian Naja naja venom on Ehrlich ascites carcinoma in BALB/c mice.

A cytotoxic and antioxidant protein (NN-32) from the Indian spectacled cobra Naja naja venom was identified and its probable mode of action on murine Ehrlich ascites carcinoma (EAC) was established. The venom purified through ion exchange chromatography produced several peaks, among which fraction 32 produced cytotoxic-cardiotoxic properties. This fraction (NN-32) showed a single peak (retention time 38.3 min) by HPLC using C4 column. The molecular mass determined by MALDI-MS, found to be 6.7 kDa and the first ten N-terminal sequence was determined (LKCNKLVPLF) by Edmann degradation method using applied Biosystem procise sequencer. It was observed that the sequence shared 100% homology with other cytotoxin cardiotoxin identified from the venom of Naja species. NN-32 showed cytotoxicity on EAC cells, increased survival time of inoculated EAC mice, reduced solid tumor volume and weight. NN-32 increased proapoptotic protein caspase 3 and 9 activity and Bax-Bcl2 ratio. It also increased the antioxidant markers glutathione, glutathione peroxidase, glutathione transferase, superoxide dismutase and catalase activity. NN-32 increased serum IL-10 level and decreased murine keratinocyte-derived chemokine level. The cardiotoxicity of NN-32 was established on isolated guinea pig auricle, where 100% irreversible blockade of auricular contraction was observed. Thus, it may be concluded that, NN-32 induced anticancer activity in EAC mice was partly mediated through its apoptogenic - antioxidant property.