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Title: Production and HPLC profiling of statins from local microbes
Authors: Bashir, Tahira
Keywords: Chemistry
Issue Date: 2019
Publisher: University of Agriculture, Faisalabad.
Abstract: Increase percent of human deaths as 30% are caused by heart diseases (CVD) by the year of 2030. The life style and uses of tobacco and alcohol are the basic reasons for abnormality in serum cholesterol level. Maintaining LDL (high density lipoprotein) level at normal range is very critical for the prevention of cardiovascular diseases (CVDs) issues. Statin drugs help to lower blood cholesterol level. Statin was synthesized from both Pleurotus and Aspergillus under solid state fermentation on three lignocellulose substrates in screening experiments for 8 days. P. spodoecus and A. terreus express maximum statin.formation i..e. 43.4 ± 1.1 mg/g and 9.1±1.4 mg/g correspondingly A study reported on O.oleariu gave 2.23 mg/g (lovastatin) under non-optimal circumstances while a study reported on O.oleariu gave 2.23 mg/g (lovastatin) under non-optimal circumstances.. RSM under CCD (Central Composite Design) was investigated for development, improvement and optimization of process that processed for statin formation through Response Surface Methodology. Four physical parameters each at five levels in CCD requiring 30 triplicate runs were done and outcome from P. spodoecus and A. terreus were measured. P. spodoecus gave highest statin yield i. e. 19 mg/g at pH 5.5, 25oC, fermentation time 144 h and inoculums size 3.5 mL on wheat straw as a growth substrate, while best statin formation obtained from A. terreus at temperature 30oC, pH 7.37, Inoculum size 4.5 mL and fermentation time 192 h was 60mg/g. Carbon and Nitrogen sources were also analyzed to show their effect on production. Highest production was achieved by using carbon source lactose and nitrogen source NaNO3) i. e. 49.3±15 mg/g before optimization. However, in A. terreus highest production was achieved with fructose and NH4NO3 i.e. 65.1±12 mg/g under pre optimized conditions. in case of P. spodoecus, optimum C/N ratio i.e. 25:1, highest statin production was achieved which was 65.7 ± 5.5 mg/g. A.terreus gave maximum production at 20:1 C/N ratio that was 78.2±9.6 mg/g. Analysis of lovastatin both in P. spodoecus and A. terreus was done by HPLC method. The lovastatin peak (lactone form) was detected at a retention time (RT) 11.2 min as compared to RT of peaks showed by standard lovastatin and samples (RT= 11.15 and 11.18) on chromatograms respectively. Hypercholesterolemia was produced in rats (Wistar) by feeding a high cholesterol diet. Group1 was normal control group, Group11 was cholesterol control group, Group 111 and groupIV were treatment groups. They were induced hypercholesterolemia by giving cholesterol rich diet from day 0 to day 30. But from days 1530, Group 111 and Group IV were given statin extracted from P. spodoecus and A . terreus correspondingly. On day 30, the values gave significant reduction in serum cholesterol level both in Gp111 treated with statin purified from P. spodoecus and groupI given purified statin extract from A. terreus source while noteably rise in serum HDL levels on 30th day in both Group111 and Group IV along with significant reduction of serum LDL levels in both treatment groups at the same time.
Gov't Doc #: 20565
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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