Biological and Phytochemical Screening of Tephrosia purpurea extract on Chemically Induced Hepatocellular Carcinoma with Reference to Biochemical Parameters

2019 ◽  
Vol 10 (02) ◽  
Author(s):  
Irfan Aziz ◽  
Birendra Shrivastava ◽  
Chandana Venkateswara Rao ◽  
Sadath Ali
Keyword(s):  
Free Radicals ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Control Group ◽  
Marker Enzymes ◽  
Tephrosia Purpurea ◽  
Single Intraperitoneal Injection ◽  
Chemically Induced ◽  
Ccl4 Treatment ◽  
Dose Dependent

Tephrosia purpurea possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Tephrosia purpurea would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Tephrosia purpurea is very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of aTephrosia purpurea of 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt.Tephrosia purpureaextract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Tephrosia purpurea extract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats.

Biological and Phytochemical Screening of Fumaria indica extract on Chemically Induced Hepatocellular Carcinoma with Reference to Biochemical Parameters

2019 ◽  
Vol 10 (02) ◽  
Author(s):  
Irfan Aziz ◽  
Birendra Shrivastava ◽  
Chandana Venkateswara Rao2 ◽  
Sadath Ali
Keyword(s):  
Free Radicals ◽  
Liver Disease ◽  
Liver Cancer ◽  
Early Stage ◽  
Food Additives ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Control Group ◽  
Industrial Chemicals ◽  
Toxic Industrial Chemicals

Liver disease or liver cancer is the sixth most common cancer and the third leading cause of cancer mortality in the world. Hepatitis viral infection, food additives, alcohol, fungal toxins (aflatoxins), toxic industrial chemicals, air and water pollutants are the major risk factors of liver cancer. Moreover, due to high tolerance of liver, HCC is seldom detected at an early stage and once detected treatment faces a poor prognosis in most cases.Fumaria indica possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Fumaria indica would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Fumaria indicais very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of a Fumaria indicaof 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt. Fumaria indica extract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Fumaria indicaextract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats. In addition to this, studies on molecular aspect of hepatoprotective therapy will give mechanistic information in hepatoprotective therapy and also critical balance should be there between the animal model and clinical research. The hepatoprotective properties of Fumaria indicashould provide useful information in the possible application in hepatic liver disease.

scholarly journals The Hepatoprotective Effect of Ethanol Extract of Syzygium campanulatum (Korth) and Syzygium aromaticum (L) Leaf on Male Wistar Rat (Rattus Norvegicus) was Induced by Paracetamol

2017 ◽  
Vol 15 (2) ◽  
pp. 196
Author(s):  
Much Ilham Novalisa Aji Wibowo ◽  
Nur Aeni ◽  
Zidna Mazayatul Huda ◽  
Nunuk Aries Nurulita
Keyword(s):  
Wistar Rats ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Hepatoprotective Activity ◽  
Group Iv ◽  
Control Group ◽  
Syzygium Aromaticum ◽  
Male Wistar Rats ◽  
Hepatoprotective Agent ◽  
Better Than

Syzygium campanulatum and Syzygium aromaticum contains antioxidant components suchas flavonoids, phenolic, and terpenoids. May have hepatoprotective properties in reducing SGPT and SGOT activity. This research wants to determine the potency of hepatoprotective of ethanolic extract of Syzygium campanulatum (Korth) and Syzygium aromaticum leaf compared with curcuma tablets. This research uses 24 male Wistar rats divided into 6 groups: I, II, III (as a normal, induction, and compared control), group IV, V, VI were treated 105, 210, and 420 mg/kg BW respectively. The study was conducted for 9 days. After 7 days of treatment, treated groups were exposed by hepatotoxic dose of paracetamol (2000 mg/kg BW). The SGPT and SGOT activity of all groups was measured by enzimatic assay. The result can be concluded that Syzygium campanulatum extract was found to be active as hepatoprotective agent with 210 mg/kg BW dosage (SGPT 21.76 ± 3.98 U/L and SGOT 7.32±6.74U/L) as eff ective as with the curcuma tablets (SGPT 23.91 ± 4.41 U/L and SGOT 14.12±5.37 U/L) and the hepatoprotective activity of Syzygium campanulatum extract at a dosage 420 mg/kg BW better than curcuma tablets (SGPT 12.43 ± 6.51 U/L and SGOT 6.64 ± 5.88 U/L). While the hepatoprotec Syzygium campanulatum and Syzygium aromaticum contains antioxidant components such as flavonoids, phenolic, and terpenoids.May have hepatoprotective properties in reducing SGPT and SGOT activity. This research wants to determine the potency of hepatoprotective of ethanolic extract of Syzygium campanulatum (Korth) and Syzygium aromaticum leaf compared with curcuma tablets. This research uses 24 male Wistar rats divided into 6 groups: I, II, III (as a normal, induction, and compared control), group IV, V, VI were treated 105, 210, and 420 mg/kg BW respectively. The study was conducted for 9 days. After 7 days of treatment, treated groups were exposed by hepatotoxic dose of paracetamol (2000 mg/kg BW). The SGPT and SGOT activity of all groups was measured by enzimatic assay. The result can be concluded that Syzygium campanulatum extract was found to be active as hepatoprotective agent with 210 mg/kg BW dosage (SGPT 21.76 ± 3.98 U/L and SGOT 7.32±6.74U/L) as eff ective as with the curcuma tablets (SGPT 23.91 ± 4.41 U/L and SGOT 14.12±5.37 U/L) and the hepatoprotective activity of Syzygium campanulatum extract at a dosage 420 mg/kg BW better than curcuma tablets (SGPT 12.43 ± 6.51 U/L and SGOT 6.64 ± 5.88 U/L). While the hepatoprotective activity of Syzygium aromaticum extracts eff ective as with curcuma tablets at all dosage variation.

HEPATOPROTECTIVE ACTIVITY OF AERIAL PARTS OF NELUMBO NUCIFERA GAERTN. IN PARACETAMOL AND ISONIAZID-RIFAMPICINE INDUCED HEPATOTOXICITY IN RATS

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (12) ◽  
pp. 47-53
Author(s):  
D Gupta ◽  
Keyword(s):  
Synergistic Effect ◽  
Group Treatment ◽  
Hepatoprotective Activity ◽  
Nelumbo Nucifera ◽  
Control Group ◽  
Aqueous Extracts ◽  
Aerial Parts ◽  
Dose Dependent

Hepatoprotective activity of ethanolic and aqueous extracts (200 and 400 mg/kg b.w.) of Nelumbo nucifera Gaertn. (NNE and NNA respectively) was evaluated by paracetamol and Isoniazid-rifampicine (INH-RMP) induced hepatotoxicity models. In paracetamol induced hepatoxicity model, NNA 400 and NNE 400 produced significant (p<0.005) reduction in SGOT level when compared to that of control group. Treatment with NNE 200, NNE 400 and NNA 400 produced significant reduction (p<0.01) in SGPT levels when compared to that of control group. SALP levels were significantly (p<0.001) reduced in animals treated with Silymarin (standard), ethanolic and aqueous extracts at both doses when compared to that of control. In INH-RMP induced hepatotoxicity model, significant (p<0.001) reduction in SGOT levels was produced in animals treated with NNA 200 and 400, NNE 200 and 400, when compared to control group animals. Ethanolic and aqueous extracts of Nelumbo nucifera at both doses produced significant (p<0.05 and 0.001 respectively) decrease in the SGPT and SALP levels when compared with control group. Hepatoprotective activity was found to be dose dependent. Significant hepatoprotective activity produced by ethanolic & aqueous extracts of Nelumbo nucifera may be a consequence of synergistic effect of the constituents present in the extracts namely, β-sitosterol and flavonoids (kaempferol, quercetin etc.) The results suggest that the ethanolic and aqueous extracts (NNE and NNA) of Nelumbo nucifera aerial parts possess significant hepatoprotective activity.

scholarly journals HEPATOPROTECTIVE ACTIVITY OF ETHANOLIC EXTRACT OF TERMINALIA CHEBULA FRUIT AGAINST ETHANOL INDUCED HEPATOTOXICITY IN RATS

2017 ◽  
Vol 10 (11) ◽  
pp. 55
Author(s):  
Balakrishna Vuyyala ◽  
Lakshmi Thakkalapally
Keyword(s):  
Ethanolic Extract ◽  
Treated Group ◽  
Hepatoprotective Activity ◽  
Control Group ◽  
Standard Group ◽  
Terminalia Chebula ◽  
Fruit Extract ◽  
Treatment Protocols ◽  
Standard Drug ◽  
Antioxidant Parameters

  Objective: The purpose of this study was to evaluate the effect of Terminalia chebula fruit extract on liver antioxidant enzymes in ethanol-induced hepatotoxicity in rats.Method: Rats were divided into six different groups each having six. Group 1 served as a control, Group 2 received 40% ethanol (2 ml/100 g, oral), in sterile water, Groups 4, 5, and 6 served as extract treatment groups and received 50, 100, and 200 mg/kg, orally, ethanolic fruit extract of T. chebula (TCE) and Group 3 served as standard group and received silymarin 25 mg/kg orally. All the treatment protocols followed 21 days, and after which rats were sacrificed, the liver was taken for antioxidant and histological studies, respectively.Results: The ethanol-treated group rats (G2) showed variable decrease in antioxidant parameter (catalase, glutathione, and glutathione reductase) levels. Administration of ethanolic TCE significantly prevented ethanol-induced elevation in the levels of malondialdehyde lipid peroxidation and decreased antioxidant parameters in experimental groups of rats. The effect of extract was compared with a standard drug, silymarin. The changes in antioxidant parameters were supported by histological profile.Conclusion: It is concluded that the ethanolic fruit TCE protects against ethanol-induced oxidative liver injury in rats.

Hepatoprotective and antioxidant activity of hydromethanolic extract of Daniella oliveri leaves in carbon tetrachloride-induced hepatotoxicity in rats

2015 ◽  
Vol 26 (5) ◽  
Author(s):  
Samuel Okwudili Onoja ◽  
Gideon Kelechi Madubuike ◽  
Maxwell Ikechukwu Ezeja
Keyword(s):  
Antioxidant Activity ◽  
Carbon Tetrachloride ◽  
Negative Control Group ◽  
Hepatoprotective Activity ◽  
Negative Control ◽  
Control Group ◽  
Photometric Assay ◽  
Dose Dependent Increase ◽  
Dose Dependent

AbstractThe hepatoprotective activity was investigated using carbon tetrachloride (CClThe pretreatment with extract (100, 200, and 400 mg/kg) and silymarin (100 mg/kg) produced a significant (p<0.05) dose-dependent increase in hepatoprotective activity when compared with the negative control group. The extract (25–400 μg/mL concentration) produced a concentration-dependent increase in antioxidant activity in 2, 2-diphenyl-1-picrylhydrazine (DPPH) photometric assay. The ICThe results of the study suggest that

scholarly journals EVALUATION OF ANTIDEPRESSANT ACTIVITY OF ETHANOLIC EXTRACT OF LAGERSTROEMIA SPECIOSA LEAVES IN ALBINO WISTAR RATS

2019 ◽  
pp. 68-74
Author(s):  
VANITA KANASE ◽  
SUNITA VISHWAKARMA
Keyword(s):  
Oxidative Stress ◽  
Normal Saline ◽  
Restraint Stress ◽  
Wistar Rats ◽  
Ethanolic Extract ◽  
Antidepressant Activity ◽  
Control Group ◽  
Dependent Manner ◽  
Lagerstroemia Speciosa ◽  
Dose Dependent

Objective: The objective of the study was to evaluate the antidepressant activity of ethanolic extract of dried leaves of Lagerstroemia speciosa L. (EELS) on acute restraint stress (ARS)-induced depression-like behavior and biochemical alterations in albino Wistar rats. Methods: Thirty rats were randomly divided into five experimental groups. Group-I (normal control) rats received normal saline (2.0 ml/kg, p.o.) daily for 14 days; Group-II (stress control) rats received normal saline (2.0 ml/kg, p.o.) daily for 14 days and subjected to restraint stress on the 13th day. Group-III (standard drug-treated) rats received imipramine (15 mg/kg, p.o.) daily for 14 days and subjected to restraint stress on the 13th day. Groups-IV and V rats were treated with EELS (100 mg/kg and 300 mg/kg, p.o.) daily for 14 days subjected to ARS on the 13th day. Stress-like behavior was assessed by subjecting the rats to behavioral paradigms such as tail-suspension test (TST) and open field test (OFT), 40 min post-restraint stress procedure. Pretest of 10 min for forced swim test (FST) was also given to each rat simultaneously. Then, 23.5 h later, the relevant samples were administered and the main test performed 30 min later. Oxidative stress parameters such as superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and extent of lipid peroxidation (LPO) were analyzed in restraint stress-induced animals and control group, following FST on the 15th day. Statistical Analysis: Expression of data was done as a mean standard error of the mean. The normally distributed data were subjected to one-way analysis of variance followed by Dunnett’s test. *p<0.05 was considered statistically significant. Results: It was observed that L. speciosa L. showed a significant dose-dependent decrease in duration of immobility time in TST and FST when compared with the control group in a dose-dependent manner. The results of OFT also showed a dose-dependent increase in locomotor activity. In addition to behavioral tests, EELS also normalized oxidative stress markers such as CAT, SOD, MDA, and LPO in a dose-dependent manner. Conclusion: The results suggest that the ethanolic extract of L. speciosa L. leaves possesses significant antidepressant property, may be recommended as a supplement for the antidepressant activity.

scholarly journals Antioxidant activity and Hepatoprotective potential of Ethanolic leaf extract of Artabotrys hexapetalus against various Hepatotoxins induced Hepatotoxicity in Albino wister Rats

2021 ◽  
Vol 12 (2) ◽  
pp. 1679-1688
Author(s):  
Suresh K ◽  
Hindustan Abdul Ahad ◽  
Satyanarayana SV
Keyword(s):  
Hydroxyl Radicals ◽  
Leaf Extract ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Alanine Transaminase ◽  
Antioxidant Function ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Ethanolic Leaf Extract ◽  
Hydroxyl Hydrogen

The objective of this research was to see whether the ethanolic extract of Artabotrys hexapetalus leaves had antioxidant and hepatoprotective properties against paracetamol (PCT), ethanol (ETN), and isoniazid and rifampicin (IR)-induced hepatotoxicity in Albino Wister rats. The materials were dried in the shade, pulverised, and extracted using ethanol. Phytochemical experiments were carried out as a first step. The ethanol extract's hepatoprotective activity was evaluated in Albino Wister rats. PCT (3 g/kg), ETN (5 g/kg), and IR (100 mg/kg) reduced the levels of SGOT, SGPT, ALP, and bilirubin, which are all biochemical indicators of liver injury. Both hepatotoxin-treated and untreated group of animals determined for their antioxidant levels. Aspartate aminotransferase (SGOT), alanine transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, an antioxidant function of DPPH (1,1-diphenyl 2-picryl hydroxyl), hydrogen peroxide (H2O2), lipid peroxidation methods, hydroxyl radicals, and nitric oxide were among the biochemical and histopathological tests performed. The altered levels of biochemical markers were restored to near-normal levels in a dose-dependent fashion after treatment with A. hexapetalus ethanolic leaf extract (100 mg/kg, 200 mg/kg, and 400 mg/kg body weight). The findings of the current research indicated that the ethanol leaf extract of A. hexapetalus had potent antioxidant and hepatoprotective properties.

scholarly journals Antioxidant Activities and Hepatoprotective Potential of Ethanol Leaf Extract of Justicia quinqueangularis against Selected Hepatotoxins Induced Hepatotoxicity in Albino Wistar Rats

2021 ◽  
pp. 24-34
Author(s):  
K. Suresh ◽  
Hindustan Abdul Ahad ◽  
S. V. Satyanarayana
Keyword(s):  
Wistar Rats ◽  
Leaf Extract ◽  
Antioxidant Activities ◽  
Ethanolic Extract ◽  
Hepatoprotective Activity ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Standard Drug ◽  
Antioxidant Function ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Background: The objective of this research was to see whether the ethanolic extract of Justicia quinqueangularis leaves had antioxidant and hepatoprotective properties against paracetamol (PCT), ethanol (ETN), and isoniazid and rifampicin (IR)-induced hepatotoxicity in Albino Wistar rats. Methods: The leaves of Justicia quinqueangularis were dried in the shade at room temperature, pulverised, and extracted by soxhlet using ethanol. Quantitative phytochemical experiments were carried out as a first step. The ethanol extract's hepatoprotective activity was evaluated in Albino Wistar rats. PCT (3 g/kg), ETN (5 g/kg), and IR (100 mg/kg) reduced the levels of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin, which are all biochemical indicators of liver injury. Both hepatotoxin-treated and untreated group of animals determined for their antioxidant levels. SGOT, SGPT, ALP, bilirubin, antioxidant function of DPPH (2,2-diphenyl-1-picrylhydrazyl), hydrogen peroxide (H2O2), lipid peroxidation methods, hydroxyl radicals, and nitric oxide scavenging activities were among the biochemical and histopathological tests performed. Results: The altered levels of biochemical markers were restored to near normal levels in a dose-dependent fashion after treatment with J. quinqueangularis ethanol leaf extract (100 mg / kg, 200 mg / kg, and 400 mg / kg body weight). Conclusion: The findings of the current research indicated that the ethanol leaf extract of J. quinqueangularis had potent antioxidant and hepatoprotective properties against standard drug.

scholarly journals Evaluation of the protective effect of Paeonia emodi Wall on rat model of Parkinson’s disease induced by 6 hydroxy dopamine

2018 ◽  
Vol 7 (11) ◽  
pp. 2137
Author(s):  
Sharmila V. Jalgaonkar ◽  
Abhay P. Kamble ◽  
Urwashi I. Parmar ◽  
Dnyaneshwar G. Kurle ◽  
Moin S. Bedrekar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuroprotective Effect ◽  
Protective Action ◽  
Ethanolic Extract ◽  
Neuroprotective Activity ◽  
Control Group ◽  
Biochemical Estimation ◽  
Dose Dependent ◽  
Muscular Coordination

Background: Generation of reactive oxygen species together with paucity of antioxidant defense is considered as an important cause for dopaminergic neuronal death. Review of literature indicates that none of the drugs so far studied for preventing the PD were found to be promising for use. Therefore, the present study was planned to evaluate the neuroprotective effect of Paeonia emodi Wall (PEW) in 6-hydroxy dopamine induced Parkinson’s disease (PD) model.Methods: The study was conducted on Wistar rats where Parkinson’s disease was induced by producing the striatal 6-hydroxy dopamine lesions. The test animals received ethanolic extract of PEW at dose of 200 and 300mg/kg for 28 days. Circling behavior, spontaneous locomotor activity, muscular coordination and akinesia were studied. Antioxidant levels were assessed by biochemical estimation and histopathology was carried out for dopaminergic neuronal loss.Results: PEW ethanolic extract showed significant dose dependent recovery in number of circlings, line crossing, muscular coordination and akinesia. A significant increase in MDA levels and decreased GSH level in PEW treated groups was observed in test groups as compared to control group (p<0.05). Normal architecture was retained only in PEW 300mg/Kg (p<0.05). L-Dopa did not showed effect on biochemical and histological parameters.Conclusions: The ethanolic extract of PEW showed neuroprotective activity against 6-hydroxy dopamine induced Parkinson’s disease in rats in both 200 and 300mg/kg doses. The protective action of PEW in PD can be because of its ability to reduce the oxidative stress.

scholarly journals ANTIASTHMATIC ACTIVITY OF THE ETHANOL EXTRACT OF LEAVES OF WRIGHTIA TINCTORIA

2018 ◽  
Vol 11 (9) ◽  
pp. 136
Author(s):  
Zaseem Khan ◽  
Imtiyaz Ansari
Keyword(s):  
Treatment Group ◽  
Intraperitoneal Injection ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Control Group ◽  
Standard Drug ◽  
Soxhlet Apparatus ◽  
Before And After ◽  
Wrightia Tinctoria ◽  
Dose Dependent

Objective: The objective of this study was to evaluate the antiasthmatic activity of ethanolic extract of Wrightia tinctoria leaves in albino wistar rats.Methods: The plant extract was taken by soxhlet apparatus with 90% ethanol. Two methods are carried out such as milk-induced leukocytosis and ovalbumin-induced leukocytosis; (4 ml/kg) milk induced as intoxicant given by subcutaneous, (4 ml/kg) ovalbumin given by intraperitoneal injection, and standard drug as dexamethasone (50 mg/kg) given for both activity and drug extract for all three test groups (low, medium, and high) blood collected from the retro-orbital plexus and count the leukocytes before and after 24 h after drug administration.Result: Test 1, Test 2, and Test 3 groups were found to significantly (**p<0.01) decrease ambulation counts as compared to milk and ovalbumin control group. The treatment group was founded to significantly (**P<0.01) milk and ovalbumin control group increases ambulation count as compared to all test groups and standard groups.Conclusion: In this study, we conclude that an ethanolic extract of the leaves of W. tinctoria possesses a significant antiasthmatic property, which is probably mediated through inhibition of histamine. The activity shown by ethanolic extract of W. tinctoria was found to be dose dependent.

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