Acute toxicity of malathion, dichlorvos and temephos in climbing perch (Anabas testudineus)

Malathion, dichlorvos and temephos are used globally to control a wide range of invertebrate pests especially in Malaysia. These pesticides usually enter aquatic environment by direct application or through overspray, runoff and watersheds. However, applications of pesticides may cause adverse impacts to many non-target organisms such as fish. The objective for this study was to determine the 96 hours lethal concentration (LC50) of each pesticide in climbing perch, Anabas testudineus. A total of 130 A. testudineus was subjected to 13 aquariums. Fish were exposed to different concentrations of each pesticide for 96 hours. Fish were observed daily and dead fish were removed immediately. The 96h LC50 value for malathion, dichlorvos and temephos was determined as 0.25 mg/L, 2.35 mg/L and 25.0 mg/L respectively. The results obtained were based on the probit analysis method as described by Finney 1952. From the values obtained, malathion, dichlorvos and temephos can be classified as highly toxic pesticides since it can kill 50 percent of the population even in lower concentration. Thus, the information in this study can be used as a guide to help environmental management to assure the effective use of these pesticides and to prevent indiscriminate use of pesticides

Anti-malarial and anti-inflammatory effects of Gynura procumbens are mediated by kaempferol via inhibition of glycogen synthase kinase-3ß (GSK3ß)

Gynura procumbens is a medicinal plant, traditionally used to treat inflammation and fever. A yeast-based assay detected GSK3â-inhibitory activity in the aqueous extract of G. procumbens. GSK3â is now known to have a central role in the modulation of host inflammatory response during bacterial infections. In this study, we investigated the involvement of GSK3â in the anti-malarial and anti-inflammatory effects of an aqueous extract of G. procumbens. Our results showed that G. procumbens inhibited growth of P. falciparum 3D7. Consecutive four-day administration of 250 mg/kg body weight (b.w.) G. procumbens resulted in strong chemosuppression and improved survivability in P. berghei-infected mice. B. pseudomallei-infected mice treated with G. procumbens (50 mg/kg b.w.) showed increased survivability. TNF-á and IFN-ã levels in liver and serum of B. pseudomallei-infected mice were lowered by G. procumbens treatment. IL-10 level was higher in serum of G. procumbens-administered infected mice. G. procumbens treatment of P. berghei-and B. pseudomallei-infected animals each resulted in increased hepatic GSK3â (Ser9) phosphorylation. It is noteworthy that kaempferol (one of the compounds in G. procumbens) also inhibited the growth of P. falciparum 3D7; showed strong chemosuppression and improved survivability in P. berghei-infected mice at 5 mg/kg b.w. B. pseudomallei-infected mice treated with kaempferol (10 mg/kg b.w.) showed improved survivability. Concomitantly, the described effects due to kaempferol also involved enhanced GSK3â (Ser9) phosphorylation as observed with G. procumbens. In summary, the observed anti-malarial and anti-inflammatory effects of G. procumbens involved inhibition of GSK3â and kaempferol may in part be responsible for the pharmacological effects

Pencirian jangkitan Plasmodium berghei NK65 pada mencit ICR sebagai model jangkitan malaria teruk

Malaria teruk atau ‘severe’ kebiasaannya disebabkan oleh jangkitan Plasmodium falciparum. Jangkitan Plasmodium falciparum pada manusia boleh menyebabkan kerosakan organ, anemia teruk, komplikasi serius, koma dan kematian. Bagi tujuan memahami patogenesis malaria teruk, model haiwan digunakan dalam kajian kali ini bagi mengenal pasti sama ada gabungan hos-parasit daripada mencit ICR dengan Plasmodium berghei NK65 boleh menyebabkan jangkitan malaria teruk pada hos. Pencirian jangkitan P. berghei ANKA pernah dilakukan sebelum ini terhadap mencit ICR; walau bagaimanapun, pencirian jangkitan P. berghei NK65 secara terperinci terhadap mencit ICR dalam kajian ini adalah pertama kali dilaporkan. Inokulasi sel darah merah (RBC) terjangkit-P. berghei NK65 (2 × 107 parasit RBC (pRBC)/ mL) dilakukan terhadap mencit ICR dengan suntikan secara intraperitoneum. Pemantauan perubahan ciri fizikal seperti berat, suhu mencit, kematian mencit, pos mortem, histologi dan aras sitokin inflamasi yang terhasil selepas jangkitan direkod untuk analisis. Strain P. berghei NK65 menghasilkan jangkitan tahap teruk terhadap mencit ICR iaitu paras parasitemia melebihi 50% pada hari ke-10 selepas jangkitan diikuti kematian. Analisis histopatologi menunjukkan jangkitan ini menyebabkan perubahan pada tisu serebrum, perlekatan leukosit pada endotelium dan pensekuesteran pRBC dalam salur darah serebrum serta pendarahan intravaskular. Selepas jangkitan, pensekuesteran pRBC dan pengumpulan pigmen malaria turut dilihat pada organ utama mencit. Tambahan lagi, edema pulmonari, pembentukan membran hialin pada peparu dan pendarahan kortikal pada ginjal dilihat pada mencit terjangkit. Sitokin proinflamasi (TNF-α, IFN-γ, dan IL-18) dan sitokin antiinflamasi (IL-10 dan IL-4) juga meningkat dalam serum mencit terjangkit. Secara rumusannya, model jangkitan mencit ICR-P. berghei NK65 yang digunakan dalam kajian ini menunjukkan ciri-ciri jangkitan malaria teruk. Hasil daripada kajian ini boleh digunakan sebagai asas untuk memahami patogenesis bagi malaria teruk pada manusia dan model jangkitan malaria haiwan pada masa akan datang

Dual Anti-Malarial and GSK3β-Mediated Cytokine-Modulating Activities of Quercetin Are Requisite of Its Potential as a Plant-Derived Therapeutic in Malaria

Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3β (GSK3β), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using Plasmodium berghei NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3β-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in P. berghei NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3β (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of P. berghei ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3β (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3β-mediated cytokine-modulating effects